Pediatric Bipolar Depression

Study identifier:D144AC00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An 8-week, Multicenter, Double-blind, Randomized, Parallel-group, Placebo-controlled Study of the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended-Release in Children and Adolescent Subjects with Bipolar Depression

Medical condition

bipolar depression

Phase

Phase 3

Healthy volunteers

Study drug

Quetiapine XR, Placebo

Sex

All

Actual Enrollment

193

Study type

Interventional

Age

10 Years - 17 Years

Date

Study Start Date: 01 Jan 2009

Primary Completion Date: 01 Nov 2010

Study Completion Date: 01 Nov 2010

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2014 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

BOGOTA D.C, Cundinamarca, Colombia

Location

Research Site

BELLO, Colombia

Location

Research Site

BOGOTA, Colombia

Location

Research Site

MEDELLIN, Colombia

Location

Research Site

VIJAYWADA, ANDH PRAD, India

Location

Research Site

AHMEDABAD, Gujarat, India

Location

Research Site

VADODARA, Gujarat, India

Location

Research Site

VARANASI, UTTAR PRAD, India

Arms	Assigned Interventions
Experimental: Quetiapine XR	Drug: Quetiapine XR Oral treatment with 150 up to 300 mg/day once daily in the evening Other Name: Seroquel XR
Placebo Comparator: Placebo	Drug: Placebo Oral treatment once daily in the evening

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted between 27 January 2009 and 1 November 2010, which included the recall visit. The recall visit occurred from 5 June 2010 till 1 November 2010.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had an up to 35-day enrollment period, 8-week double-blind treatment period with 1 of 2 treatment regimens (quetiapine XR 150 to 300 mg/day or placebo), 1-week safety follow-up period, 2- to 4-week safety follow-up period for patients with BP >95th percentile at completion/discontinuation.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Participant Flow: Overall Study

	Quetiapine XR	Placebo
STARTED	93	100
COMPLETED	70	74
NOT COMPLETED	23	26
Adverse Event	3	12
Lost to Follow-up	5	1
Withdrawal by Subject	2	4
Severe non-compliance to protocol	2	4
Lack of therapeutic response	4	1
Condition under investigation worsened	1	3
Other 2	4	1
Incorrect Enrollment	1	0
Safety Reasons	1	0

Baseline Characteristics

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

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Baseline Measures

	Quetiapine XR	Placebo	Total
Number of Participants [units: Participants]	92	100	192
Age Continuous ^[1] [units: years] Mean ± Standard Deviation	13.9 ± 2.18	14.0 ± 2.05	14.0 ± 2.11
Gender, Male/Female ^[2] [units: participants]
Female	47	48	95
Male	45	52	97

Outcome Measures

1. Primary Outcome Measure: Change in the Children Depression Rating Scale, Revised (CDRS-R) total score from baseline to final assessment (Day 57) [ Time Frame: Will be scored at all visits. the analysis is the change from baseline to the final assessment at day 57 ]

Measure Type	Primary
Measure Name	Change in the Children Depression Rating Scale, Revised (CDRS-R) total score from baseline to final assessment (Day 57)
Measure Description	Severity of depression in children and adolescents was calculated based on the 17-item CDRS-R scale (3 items scored from 1-5 and 14 items scored from 1-7, with higher scores indicating more severe depression). The 17 item scores are summed to give the total score (total score range 17-113).
Time Frame	Will be scored at all visits. the analysis is the change from baseline to the final assessment at day 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
Change in the Children Depression Rating Scale, Revised (CDRS-R) total score from baseline to final assessment (Day 57) [units: Scores on a scale] Least Squares Mean (Standard Error)	-29.6 (1.65)	-27.3 (1.60)

No statistical analysis provided for Change in the Children Depression Rating Scale, Revised (CDRS-R) total score from baseline to final assessment (Day 57)

2. Secondary Outcome Measure: Number of patients reaching remission where remission is defined as CDRS-R total score ≤28 at final assessment (Day 57). [ Time Frame: Days 8 to 57 ]

Measure Type	Secondary
Measure Name	Number of patients reaching remission where remission is defined as CDRS-R total score ≤28 at final assessment (Day 57).
Measure Description	The number of patients with remission from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113).
Time Frame	Days 8 to 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
Number of patients reaching remission where remission is defined as CDRS-R total score ≤28 at final assessment (Day 57). [units: participants]	42	34

No statistical analysis provided for Number of patients reaching remission where remission is defined as CDRS-R total score ≤28 at final assessment (Day 57).

3. Secondary Outcome Measure: The number of patients with the response, where response is defined as ≥50% reduction from baseline to final assessment (Day 57) in CDRS-R total score [ Time Frame: Days 8 to 57 ]

Measure Type	Secondary
Measure Name	The number of patients with the response, where response is defined as ≥50% reduction from baseline to final assessment (Day 57) in CDRS-R total score
Measure Description	The number of patients reaching response from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113).
Time Frame	Days 8 to 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
The number of patients with the response, where response is defined as ≥50% reduction from baseline to final assessment (Day 57) in CDRS-R total score [units: participants]	58	55

No statistical analysis provided for The number of patients with the response, where response is defined as ≥50% reduction from baseline to final assessment (Day 57) in CDRS-R total score

4. Secondary Outcome Measure: Change from baseline to final assessment (Day 57) in the CGI-BP-S [ Time Frame: Change from Baseline to Day 57 ]

Measure Type	Secondary
Measure Name	Change from baseline to final assessment (Day 57) in the CGI-BP-S
Measure Description	The CGI-BP-S scale rates the severity of the patient’s illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity.
Time Frame	Change from Baseline to Day 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
Change from baseline to final assessment (Day 57) in the CGI-BP-S [units: Scores on a Scale] Least Squares Mean (Standard Error)	-17.2 (0.15)	-1.35 (0.14)

No statistical analysis provided for Change from baseline to final assessment (Day 57) in the CGI-BP-S

5. Secondary Outcome Measure: CGI-BP-C score at final assessment (Day 57) [ Time Frame: Change from Baseline to day 57 ]

Measure Type	Secondary
Measure Name	CGI-BP-C score at final assessment (Day 57)
Measure Description	The CGI-BP-C scale rates how much the patient’s illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). CGI-BP-C scores >4 indicate worsening, while scores <4 indicate improvement.
Time Frame	Change from Baseline to day 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
CGI-BP-C score at final assessment (Day 57) [units: Scores on a scale] Least Squares Mean (Standard Error)	2.4 (0.15)	2.6 (0.15)

No statistical analysis provided for CGI-BP-C score at final assessment (Day 57)

6. Secondary Outcome Measure: The proportion of patients at final assessment (Day 57) with improvement of overall bipolar illness [ Time Frame: Day 57 ]

Measure Type	Secondary
Measure Name	The proportion of patients at final assessment (Day 57) with improvement of overall bipolar illness
Measure Description	The proportion of patients with improvement of overall bipolar illness at Day 57 was calculated. Improvement defined as a CGI-BP-C of “Much” or “Very much” improved in overall bipolar illness assessment.
Time Frame	Day 57
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.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Measured Values

	Quetiapine XR	Placebo
Number of Participants Analyzed [units:participants]	92	100
The proportion of patients at final assessment (Day 57) with improvement of overall bipolar illness [units: Proportions]	0.522	0.40

No statistical analysis provided for The proportion of patients at final assessment (Day 57) with improvement of overall bipolar illness

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Serious Adverse Events

Quetiapine XR

Placebo

Total, serious adverse events

# participants affected / at risk

1/---

4/---

Psychiatric disorders

Agitation¹,^†

# participants affected / at risk

1/---

0/---

Social circumstances

Social Stay Hospitalisation²,^†

# participants affected / at risk

0/---

1/---

Psychiatric disorders

Bipolar Disorder²,^†

# participants affected / at risk

0/---

1/---

Psychiatric disorders

Aggression²,^†

# participants affected / at risk

0/---

1/---

Psychiatric disorders

Depressive Symptoms²,^†

# participants affected / at risk

0/---

1/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary, MedDRA (12.0)
3	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Quetiapine XR	Quetiapine XR 150 to 300mg once a day
Placebo	Matching placebo

Other Adverse Events

Quetiapine XR

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

68/92 (73.91%)

66/100 (66.00%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

20/92 (21.74%)

12/100 (12.00%)

Nervous system disorders

Sedation¹,^†

# participants affected / at risk

7/92 (7.61%)

6/100 (6.00%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

6/92 (6.52%)

2/100 (2.00%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

6/92 (6.52%)

4/100 (4.00%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

4/92 (4.35%)

1/100 (1.00%)

Infections and infestations

Nasoparyngitis¹,^†

# participants affected / at risk

4/92 (4.35%)

3/100 (3.00%)

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

3/92 (3.26%)

0/100 (0.00%)

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

3/92 (3.26%)

0/100 (0.00%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

3/92 (3.26%)

0/100 (0.00%)

Infections and infestations

Ear Infection¹,^†

# participants affected / at risk

2/92 (2.17%)

0/100 (0.00%)

Infections and infestations

Upper respiratory Tract Infection¹,^†

# participants affected / at risk

1/92 (1.09%)

2/100 (2.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/92 (5.43%)

1/100 (1.00%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

5/92 (5.43%)

1/100 (1.00%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/92 (3.26%)

3/100 (3.00%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

2/92 (2.17%)

3/100 (3.00%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

2/92 (2.17%)

1/100 (1.00%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/92 (2.17%)

1/100 (1.00%)

Gastrointestinal disorders

Gastrooesophageal Reflux Disease¹,^†

# participants affected / at risk

2/92 (2.17%)

0/100 (0.00%)

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

5/92 (5.43%)

2/100 (2.00%)

General disorders and administration site conditions

Irritability¹,^†

# participants affected / at risk

2/92 (2.17%)

5/100 (5.00%)

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

2/92 (2.17%)

1/100 (1.00%)

General disorders and administration site conditions

Thirst¹,^†

# participants affected / at risk

2/92 (2.17%)

0/100 (0.00%)

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/92 (0.00%)

2/100 (2.00%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

2/92 (2.17%)

0/100 (0.00%)

Psychiatric disorders

Nightmare¹,^†

# participants affected / at risk

2/92 (2.17%)

2/100 (2.00%)

Psychiatric disorders

Aggression¹,^†

# participants affected / at risk

0/92 (0.00%)

2/100 (2.00%)

Metabolism and nutrition disorders

Increased Appetite¹,^†

# participants affected / at risk

3/92 (3.26%)

3/100 (3.00%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

2/92 (2.17%)

2/100 (2.00%)

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

3/92 (3.26%)

0/100 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/92 (0.00%)

3/100 (3.00%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal Pain¹,^†

# participants affected / at risk

0/92 (0.00%)

2/100 (2.00%)

Reproductive system and breast disorders

Dysmenorrhoea¹,^†

# participants affected / at risk

2/92 (2.17%)

2/100 (2.00%)

Skin and subcutaneous tissue disorders

Dermatitis Contact¹,^†

# participants affected / at risk

2/92 (2.17%)

1/100 (1.00%)

Injury, poisoning and procedural complications

Orthodontic Appliance Complication¹,^†

# participants affected / at risk

0/92 (0.00%)

2/100 (2.00%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/92 (0.00%)

2/100 (2.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (12.0)
2	Term from vocabulary,

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:

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
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

CSR-D144AC00001.pdf
Download
CSR-D144AC00001.pdf
Download
D144AC00001_Redacted_Study_Protocol
Download
Trial Results Summaries
Available here

Contacts

Contact

Quintiles Worldwide

Clinical.studies.ns@quintiles.com

Investigators

Principal Investigator

Michael Castiglione

AstraZeneca Pharmaceuticals

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR-D144AC00001.pdf

CSR-D144AC00001.pdf

D144AC00001_Redacted_Study_Protocol

Trial Results Summaries