Faslodex in McCune-Albright Syndrome - FMAS

Study identifier:D6992C00044

ClinicalTrials.gov identifier:NCT00278915

EudraCT identifier:2005-004893-26

CTIS identifier:N/A

Study Complete

Official Title

An Open-label, Non-Comparative Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Faslodex (fulvestrant) in Girls with Progressive Precocious Puberty Associated with McCune-Albright Syndrome

Medical condition

Puberty, Precocious, McCune-Albright Syndrome

Phase

Phase 2

Healthy volunteers

Study drug

Fulvestrant

Sex

Female

Actual Enrollment

Study type

Interventional

Age

1 Years - 10 Years

Date

Study Start Date: 31 Jan 2006

Primary Completion Date: 08 Dec 2009

Study Completion Date: 20 Jul 2023

Study design

Allocation: N/A
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Bron, France, 69677

Location

Research Site

Paris Cedex 12, France, 75571

Location

Research Site

Baton Rouge, LA, United States, 70808

Location

Research Site

London, United Kingdom, WC1N 3JH

Location

Research Site

Erlangen, Germany, 91054

Location

Research Site

Miami, FL, United States, 33136

Location

Research Site

Lexington, KY, United States, 40508

Location

Research Site

Bordeaux, France, 33000

Arms	Assigned Interventions
Experimental: Fulvestrant Participants will receive intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants will be dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants will be dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.	Drug: Fulvestrant Participants will receive intramuscular injection of fulvestrant as stated in arm description. Other Name: Faslodex Other Name: ZD9238

Arms

Assigned Interventions

Experimental: Fulvestrant
Participants will receive intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants will be dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants will be dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Drug: Fulvestrant
Participants will receive intramuscular injection of fulvestrant as stated in arm description.

Other Name: Faslodex

Other Name: ZD9238

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at study sites located in France, Germany, Italy, Russian Federation, United Kingdom, and the United States of America.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 30 participants were enrolled in this study.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Participant Flow: Overall Study

	Fulvestrant
STARTED	30
COMPLETED	29
NOT COMPLETED	1
Disease progression	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The full-analysis set (FAS) population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Baseline Measures

	Fulvestrant
Number of Participants [units: Participants]	30
Age Continuous [units: Years] Mean ± Standard Deviation	5.86 ± 1.846
Sex: Female, Male [units: Participants]
Female	30
Male	0
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	26
More than one race	2
Unknown or Not Reported	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	3
Not Hispanic or Latino	4
Unknown or Not Reported	23

Outcome Measures

1. Primary Outcome Measure: Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period ]

Measure Type	Primary
Measure Name	Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline
Measure Description	Vaginal bleeding days are defined as the number of days in which vaginal bleeding, (including spotting) occurred. In order to annualize, a 12-month period is defined as 360 days and a 6-month period is defined as 180 days. Frequency of annualized vaginal bleeding days = [(number of vaginal bleeding days)/(total number of days of the time interval under consideration)] multiplied by 360. Change in frequency is equal to the on-treatment frequency minus the baseline frequency. Diary cards will capture days of vaginal bleeding during the 12-month treatment period. Change in the frequency of annualized days of vaginal bleeding during the 12-month treatment period compared to the 6-month baseline period, based on a worst-case scenario calculation (ie, missing diary card days counted as bleeding days) are reported.
Time Frame	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full-analysis set (FAS) population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline [units: Days per year] Median (Full Range)	-3.6 (-42 to 185)

No statistical analysis provided for Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline

2. Primary Outcome Measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period ]

Measure Type	Primary
Measure Name	Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline
Measure Description	The percentage change in frequency is defined as 100% times the difference (the on-treatment period frequency minus the baseline period frequency), divided by the baseline period frequency. The percentage of participants with baseline vaginal bleeding days who experienced ≥ 50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Time Frame	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6 month baseline period.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	23
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline [units: Percentage of Participants] Number (95% Confidence Interval)	73.9 (51.6 to 89.8)

No statistical analysis provided for Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline

3. Primary Outcome Measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period [ Time Frame: Baseline (6-month pre-treatment observation period) through Month 12 treatment period ]

Measure Type	Primary
Measure Name	Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period
Measure Description	Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 6-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Time Frame	Baseline (6-month pre-treatment observation period) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6-month baseline period.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	23
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period [units: Percentage of Participants] Number (95% Confidence Interval)	78.3 (56.3 to 92.5)

No statistical analysis provided for Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period

4. Primary Outcome Measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period [ Time Frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period ]

Measure Type	Primary
Measure Name	Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period
Measure Description	Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 12-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Time Frame	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6 month baseline period.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	23
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period [units: Percentage of Participants] Number (95% Confidence Interval)	34.8 (16.4 to 57.3)

No statistical analysis provided for Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period

5. Primary Outcome Measure: Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6-month pre-treatment observation period) through Month 6 of treatment period ]

Measure Type	Primary
Measure Name	Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline
Measure Description	Change in rate of BA advancement over first 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in chronological age (CA) (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between BA radiograph dates. It is calculated as [(BA6 – BA0)/(CA6 – CA0)] – [(BA0 – BA)/(CA0 – CA)], where 6, 0, * stand for first Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Time Frame	Baseline (6-month pre-treatment observation period) through Month 6 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline [units: Ratio] Mean (Standard Deviation)	-0.83 (1.507)

No statistical analysis provided for Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline

6. Primary Outcome Measure: Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period ]

Measure Type	Primary
Measure Name	Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline
Measure Description	Change in rate of BA advancement over second 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as [(BA6 – BA0)/(CA6 – CA0)] – [(BA0 – BA)/(CA0 – CA)], where 6, 0, * stand for second Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Time Frame	Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	29
Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline [units: Ratio] Mean (Standard Deviation)	-1.10 (1.383)

No statistical analysis provided for Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline

7. Primary Outcome Measure: Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6-month pre-treatment observation period) through Month 12 of treatment period ]

Measure Type	Primary
Measure Name	Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline
Measure Description	Change in rate of BA advancement over whole 12-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as [(BA12 – BA0) / (CA12 – CA0)] – [(BA0 – BA) / (CA0 – CA)], where 12, 0, * stand for Month 12 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Time Frame	Baseline (6-month pre-treatment observation period) through Month 12 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline [units: Ratio] Mean (Standard Deviation)	-0.93 (1.343)

No statistical analysis provided for Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline

8. Primary Outcome Measure: Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over First 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through first 6-month of treatment period ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over First 6-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to first 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Time Frame	Baseline (6 month pre-treatment observation period) through first 6-month of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over First 6-month Treatment Period Compared to Baseline [units: cm/year] Mean (Standard Deviation)	-1.7 (4.35)

No statistical analysis provided for Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over First 6-month Treatment Period Compared to Baseline

9. Primary Outcome Measure: Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Second 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period) ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Second 6-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to second 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Time Frame	Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Second 6-month Treatment Period Compared to Baseline [units: cm/year] Mean (Standard Deviation)	-0.8 (4.49)

No statistical analysis provided for Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Second 6-month Treatment Period Compared to Baseline

10. Primary Outcome Measure: Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Whole 12-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Whole 12-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to the 12-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Time Frame	Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

	Description
Fulvestrant	Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Whole 12-month Treatment Period Compared to Baseline [units: cm/year] Mean (Standard Deviation)	-1.4 (3.69)

No statistical analysis provided for Change in Growth Velocity (Annualized Growth Velocity in cm/year) Over Whole 12-month Treatment Period Compared to Baseline

11. Primary Outcome Measure: Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through first 6-month treatment period ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (Z-score) from baseline period to the first 6 months of treatment period is reported. The Z-score (also known as Standard Deviation Score [SDS]) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by standard deviation (SD)], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Time Frame	Baseline (6 month pre-treatment observation period) through first 6-month treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline [units: Unit on a score] Mean (Standard Deviation)	-1.60 (4.616)

No statistical analysis provided for Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline

12. Primary Outcome Measure: Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (Z-score) from baseline period to the second 6 months of treatment period is reported. The Z-score (also known as SDS) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Time Frame	Baseline (6 month pre-treatment observation period) through second 6-month treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline [units: Unit on a score] Mean (Standard Deviation)	-0.64 (4.606)

No statistical analysis provided for Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline

13. Primary Outcome Measure: Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline [ Time Frame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period ]

Measure Type	Primary
Measure Name	Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline
Measure Description	Change in growth velocity (Z-score) from baseline period to 12 months of treatment period is reported. The Z-score (also known as SDS) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD)], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Time Frame	Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline [units: Unit on a score] Mean (Standard Deviation)	-1.14 (4.078)

No statistical analysis provided for Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline

14. Primary Outcome Measure: Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound [ Time Frame: Baseline (pre-treatment baseline visit) and Month 6 of treatment period ]

Measure Type	Primary
Measure Name	Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound
Measure Description	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 6 was calculated as Month 6 volume (by ultrasound) minus screening visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.
Time Frame	Baseline (pre-treatment baseline visit) and Month 6 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	29
Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound [units: Cubic centimeters] Median (Full Range)	-1.10 (-15.10 to 6.04)

No statistical analysis provided for Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound

15. Primary Outcome Measure: Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound [ Time Frame: At Month 6 and Month 12/final visit treatment period ]

Measure Type	Primary
Measure Name	Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound
Measure Description	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from Month 6 to Month 12/final visit was calculated as Month 12/finial visit volume (by ultrasound) minus Month 6 volume (by ultrasound).
Time Frame	At Month 6 and Month 12/final visit treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	28
Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound [units: Cubic centimetres] Median (Full Range)	-0.13 (-11.84 to 4.48)

No statistical analysis provided for Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound

16. Primary Outcome Measure: Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound [ Time Frame: Baseline (pre-treatment screening visit) and Month 12 treatment period ]

Measure Type	Primary
Measure Name	Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound
Measure Description	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 12/final visit was calculated as End of Study volume (by ultrasound) minus Screening Visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.
Time Frame	Baseline (pre-treatment screening visit) and Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	27
Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound [units: Cubic centimeters] Median (Full Range)	-2.44 (-10.20 to 6.56)

No statistical analysis provided for Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound

17. Primary Outcome Measure: Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound [ Time Frame: Baseline (pre-treatment screening visit) and Month 6 of treatment period ]

Measure Type	Primary
Measure Name	Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound
Measure Description	The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to Month 6 was calculated as Month 6 mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.
Time Frame	Baseline (pre-treatment screening visit) and Month 6 of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	25
Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound [units: Cubic centimetres] Median (Full Range)	0.10 (-27.62 to 7.96)

No statistical analysis provided for Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound

18. Primary Outcome Measure: Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound [ Time Frame: At Month 6 and Month 12/final visit treatment period ]

Measure Type	Primary
Measure Name	Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound
Measure Description	The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from Month 6 to Month 12/final visit was calculated as Month 12/final visit mean volume minus Month 6 mean volume.
Time Frame	At Month 6 and Month 12/final visit treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	24
Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound [units: Cubic centimetres] Median (Full Range)	0.76 (-4.08 to 9.97)

No statistical analysis provided for Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound

19. Primary Outcome Measure: Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound [ Time Frame: Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period ]

Measure Type	Primary
Measure Name	Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound
Measure Description	The mean ovarian volume was the average of both ovaries. Average ovarian volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to the end of the study was calculated as End of Study mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.
Time Frame	Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	21
Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound [units: Cubic centimetres] Median (Full Range)	1.01 (-22.25 to 10.36)

No statistical analysis provided for Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound

20. Primary Outcome Measure: Mean Clearance of Fulvestrant [ Time Frame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose ]

Measure Type	Primary
Measure Name	Mean Clearance of Fulvestrant
Measure Description	Mean clearance of fulvestrant is reported.
Time Frame	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Mean Clearance of Fulvestrant [units: Litres/hour] Mean (Standard Deviation)	38.4 (11.56)

No statistical analysis provided for Mean Clearance of Fulvestrant

21. Primary Outcome Measure: Mean Volume of Distribution (V1/F) of Fulvestrant [ Time Frame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose ]

Measure Type	Primary
Measure Name	Mean Volume of Distribution (V1/F) of Fulvestrant
Measure Description	Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V1/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.
Time Frame	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population PK analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Mean Volume of Distribution (V1/F) of Fulvestrant [units: Litres] Mean (Standard Error)	33000 (NA)^[1]

No statistical analysis provided for Mean Volume of Distribution (V1/F) of Fulvestrant

22. Primary Outcome Measure: Mean Volume of Distribution (V2/F) of Fulvestrant [ Time Frame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose ]

Measure Type	Primary
Measure Name	Mean Volume of Distribution (V2/F) of Fulvestrant
Measure Description	Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V2/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.
Time Frame	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population PK analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Mean Volume of Distribution (V2/F) of Fulvestrant [units: Litres] Mean (Standard Error)	32700 (NA)^[1]

No statistical analysis provided for Mean Volume of Distribution (V2/F) of Fulvestrant

23. Primary Outcome Measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through 68.7 weeks (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	Day 1 through 68.7 weeks (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [units: Participants]
Any TEAEs	27
Any TESAEs	9

No statistical analysis provided for Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

24. Primary Outcome Measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [ Time Frame: Day 1 through 68.7 weeks (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Measure Description	Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Clinical laboratory parameter analysis included hematology and clinical chemistry.
Time Frame	Day 1 through 68.7 weeks (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [units: Participants]
Anemia	1
Vitamin D Deficiency	1

No statistical analysis provided for Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

25. Primary Outcome Measure: Number of Participants With Compliance to Study Treatment [ Time Frame: Day 1 through Month 12 of treatment period ]

Measure Type	Primary
Measure Name	Number of Participants With Compliance to Study Treatment
Measure Description	Number of participants with compliance to study treatment are reported. Treatment compliance was ensured at each treatment visit whether each participant received all protocol-defined injections up until the point they either withdrew from the study or completed the main study period. Compliance with study treatment for each participant for the 12-month treatment period was calculated as total number of injections divided by number of visits between first injection (Month 0) and last injection (at Month 11).
Time Frame	Day 1 through Month 12 of treatment period
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Number of Participants With Compliance to Study Treatment [units: Participants]	30

No statistical analysis provided for Number of Participants With Compliance to Study Treatment

26. Primary Outcome Measure: Number of Participants With Withdrawals from Study Treatment due to TEAE [ Time Frame: Day 1 through 68.7 weeks (maximum observed duration) ]

Measure Type	Primary
Measure Name	Number of Participants With Withdrawals from Study Treatment due to TEAE
Measure Description	Number of participants with withdrawals from study treatment due to TEAE are reported.
Time Frame	Day 1 through 68.7 weeks (maximum observed duration)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Number of Participants With Withdrawals from Study Treatment due to TEAE [units: Participants]	0

No statistical analysis provided for Number of Participants With Withdrawals from Study Treatment due to TEAE

27. Primary Outcome Measure: Hormone Assay: Serum Oestradiol Level [ Time Frame: Month 12 (final visit) of treatment period ]

Measure Type	Primary
Measure Name	Hormone Assay: Serum Oestradiol Level
Measure Description	Serum oestradiol level at Month 12 (final visit) is reported.
Time Frame	Month 12 (final visit) of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
he FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	26
Hormone Assay: Serum Oestradiol Level [units: pmol/L] Mean (Standard Deviation)	25.95 (30.718)

No statistical analysis provided for Hormone Assay: Serum Oestradiol Level

28. Primary Outcome Measure: Hormone Assay: Serum Luteinizing Hormone (LH) Level [ Time Frame: Month 12 (final visit) of treatment period ]

Measure Type	Primary
Measure Name	Hormone Assay: Serum Luteinizing Hormone (LH) Level
Measure Description	Serum LH level collected at Month 12 (final visit) is reported.
Time Frame	Month 12 (final visit) of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	28
Hormone Assay: Serum Luteinizing Hormone (LH) Level [units: IU/L] Mean (Standard Deviation)	0.11 (0.042)

No statistical analysis provided for Hormone Assay: Serum Luteinizing Hormone (LH) Level

29. Primary Outcome Measure: Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level [ Time Frame: Month 12 (final visit) of treatment period ]

Measure Type	Primary
Measure Name	Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level
Measure Description	Serum FSH level collected at Month 12 (final visit) is reported.
Time Frame	Month 12 (final visit) of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	29
Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level [units: IU/L] Mean (Standard Deviation)	1.13 (1.024)

No statistical analysis provided for Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level

30. Primary Outcome Measure: Hormone Assay: Serum Testosterone Level [ Time Frame: Month 12 (final visit) of treatment period ]

Measure Type	Primary
Measure Name	Hormone Assay: Serum Testosterone Level
Measure Description	Serum testosterone level at Month 12 (final visit) is reported.
Time Frame	Month 12 (final visit) of treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	28
Hormone Assay: Serum Testosterone Level [units: nmol/L] Mean (Standard Deviation)	0.65 (0.273)

No statistical analysis provided for Hormone Assay: Serum Testosterone Level

31. Secondary Outcome Measure: Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit [ Time Frame: From Baseline (Month 0) through Month 12 treatment period ]

Measure Type	Secondary
Measure Name	Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit
Measure Description	Change in Tanner stage (measure of pubertal progression) of breast from baseline to Month 12/last visit is reported. Tanner stage (breast) is a score of range 1-5 where 1 = no development and 5 = adult breast.
Time Frame	From Baseline (Month 0) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit [units: Unit on a scale] Median (Full Range)	0.0 (-3 to 2)

No statistical analysis provided for Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit

32. Secondary Outcome Measure: Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit [ Time Frame: From Baseline (Month 0) through Month 12 treatment period ]

Measure Type	Secondary
Measure Name	Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit
Measure Description	Change in Tanner stage (measure of pubertal progression) of pubic hair from baseline to Month 12/final visit is reported. Tanner stage (pubic hair) is a score of range 1-5 where 1 = no development and 5 = adult pubic hair.
Time Frame	From Baseline (Month 0) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit [units: Unit on a scale] Median (Full Range)	0.0 (-2 to 1)

No statistical analysis provided for Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit

33. Secondary Outcome Measure: Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit [ Time Frame: From Baseline (screening visit) through Month 12 treatment period ]

Measure Type	Secondary
Measure Name	Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit
Measure Description	Change in PAH for children over age 6 is reported. Bone age radiographs were collected retrospectively. PAH equals the current height divided by a factor (the fraction of final adult height) based on current bone age (central read) and current bone age relative to chronological age, classified as retarded, average or advanced. Retarded is defined as current bone age (years) < chronological age (years) minus 1; advanced is defined as current bone age (years) > chronological age (years) plus 1; otherwise, bone age is classified as average. The PAH was summarized using the Bayley and Pinneau method.
Time Frame	From Baseline (screening visit) through Month 12 treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were analyzed for this endpoint.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	17
Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit [units: Centimeter] Mean (Standard Deviation)	0.5 (4.10)

No statistical analysis provided for Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit

34. Secondary Outcome Measure: Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation [ Time Frame: Baseline (screening) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation
Measure Description	The MAS is caused by an activating mutation in the gene coding for the stimulatory subunit of the G protein, Gsα. The altered Gsα causes autonomous activation of G-protein stimulated cyclic adenosine monophosphate (cAMP) formation, which in the gonads, results in episodic uncontrolled sex steroid production and subsequent pubertal development. For participants who provided separate specific informed consent, the percentage of participants with a Gsα mutation at screening was assessed by molecular analysis of peripheral blood.
Time Frame	Baseline (screening)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Measured Values

	Fulvestrant
Number of Participants Analyzed [units:participants]	30
Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation [units: Percentage of participants]	23.3

No statistical analysis provided for Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation

Serious Adverse Events

Time Frame	Day 1 through 68.7 weeks (maximum observed duration)
Additional Description	The FAS population included participants who received at least 1 dose of study drug.

Reporting Groups

Description

Fulvestrant

Serious Adverse Events

Fulvestrant

Total, serious adverse events

# participants affected / at risk

9/30 (30.00%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Infections and infestations

Viral Infection¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Injury, poisoning and procedural complications

Femur Fracture¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Musculoskeletal and connective tissue disorders

Bone Pain¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Nervous system disorders

Neuromyopathy¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Psychiatric disorders

Tic¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Reproductive system and breast disorders

Ovarian Cyst¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

1/30 (3.33%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1

Other Adverse Events

Time Frame	Day 1 through 68.7 weeks (maximum observed duration)
Additional Description	The FAS population included participants who received at least 1 dose of study drug.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

Description

Fulvestrant

Other Adverse Events

Fulvestrant

Total, other (not including serious) adverse events

# participants affected / at risk

25/30 (83.33%)

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

14/30 (46.67%)

# events

General disorders

Injection Site Inflammation¹,^†

# participants affected / at risk

4/30 (13.33%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

General disorders

Injection Site Pain¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

8/30 (26.67%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

8/30 (26.67%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/30 (16.67%)

# events

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

4/30 (13.33%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/30 (26.67%)

# events

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

7/30 (23.33%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal Pain¹,^†

# participants affected / at risk

4/30 (13.33%)

# events

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

6/30 (20.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Ear Infection¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Infections and infestations

Otitis Media¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Pharyngitis Streptococcal¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

H1N1 Influenza¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Tonsillitis¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

5/30 (16.67%)

# events

Infections and infestations

Vaginal Infection¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Varicella¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

5/30 (16.67%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Musculoskeletal and connective tissue disorders

Bone Pain¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Musculoskeletal and connective tissue disorders

Neck Pain¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Ear and labyrinth disorders

Ear Pain¹,^†

# participants affected / at risk

4/30 (13.33%)

# events

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

3/30 (10.00%)

# events

Skin and subcutaneous tissue disorders

Eczema¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Respiratory, thoracic and mediastinal disorders

Productive Cough¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Vascular disorders

Hot Flush¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

General disorders

Injection Site Reaction¹,^†

# participants affected / at risk

2/30 (6.67%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

4/30 (13.33%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Data for exploration on body weight and race effect on fulvestrant PK is not available due to small sample size. Data for number and size of ovarian cysts at different time-point were too sparse to produce a meaningful summary, hence not reported.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical study Information Center
Phone	+1-877-240-9479
E-mail:	[email protected]

Documents available

CSR-D6992C00044.pdf
Download
CSR Synopsis Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

AstraZeneca Faslodex Medical Science Director

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site