A Study to Evaluate the Effect of a Single-Dose Intravenous Administration of MEDI-528

Study identifier:MI-CP139

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase2A, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of a Single-Dose Intravenous Administration of MEDI-528, A Humanized Anti-Interleukin-9 Monoclonal Antibody, on Allergen-Induced Interleukin-9 Levels in Bronchoalveolar Lavage Fluid in Adults with Atopic Asthma

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 50 Years

Date

Study Start Date: 01 Jul 2007

Primary Completion Date: 01 Oct 2008

Study Completion Date: 01 Jun 2009

Study design

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

Verification:

Verified 01 Feb 2014 by MedImmune

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Male or female adults, age 18 through 50 years of age at time of screening;
- Written informed consent obtained from the patient prior to receipt of any study medication or beginning any study procedures;
- Previously documented diagnosis of asthma based on episodic symptoms of airflow obstruction such as wheezing or chest tightness, with alternative diagnoses (eg, chronic obstructive pulmonary disease) ruled out;
- Forced expiratory volume in one second (FEV1) ≥ 70% of predicted value;
- A positive skin prick or intradermal test to cat allergen extract, short ragweed allergen extract, or dust mite allergen extracts. A positive skin test is defined as the indurations of skin test wheal being at least 2 mm greater in diameter than that of the indurations of the control skin wheal;
- History of asthmatic symptoms upon exposure to at least one of the allergens (cat allergen extract, short ragweed allergen extract, or dust mite allergen extracts) that induces a positive skin prick test;
- AHR on methacholine inhalation challenge test, with PC20 ≤ 8 mg/mL (Crapo, 2000);
- No significant changes in regular asthma medications and no acute asthma exacerbations requiring oral corticosteroids or doubling of ICS dosage, hospitalization, emergency room visits, or unscheduled health care provider visits for asthma for at least 6 weeks prior to screening and up through the time of study drug administration;
- No history of intubation or admission to an intensive care unit for asthma;
- Sexually active women, unless surgically sterile or at least 1 year post-menopausal, must have used an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 21 days prior to the study drug administration on Study Day 0, and must agree to continue using such precautions through Study Day 126. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active men, unless surgically sterile, must likewise use an effective method of birth control (condom) and must agree to continue using such precautions through Study Day 126;
- Able to follow study procedures including the ability to provide spirometry readings that meet American Thoracic Society (ATS)/European Respiratory Society (ERS) standards (Miller, 2005);
- Ability to complete the study period, including follow-up period, of up to 126 days; and
- Willing to forego other forms of experimental treatment and study procedures during study.

Exclusion Criteria

- Receipt of MEDI-528 in any previous clinical study;
- History of allergy or reaction to any component of the study drug formulation or other medications, such as topical lidocaine, administered during bronchoscopy;
- Lung disease other than allergic asthma (eg, chronic bronchitis);
- FEV1 < 70% of predicted values;
- Use of systemic immunosuppressive drugs including systemic corticosteroids (topical corticosteroids are permitted), ICS at doses > 800 μg/day budesonide or equivalent, long-acting β2 agonists (eg, salmeterol), leukotriene antagonists, cromolyn sodium, nedocromil sodium, theophylline, omalizumab, or any other medication for asthma except short-acting β2 agonist (as needed) within the 4 weeks prior to screening up through administration of study drug;
- Current use of any β-adrenergic antagonist (eg, propranolol);
- Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period;
- Upper or lower respiratory tract infections within 8 weeks before screening;
- Acute illnesses or evidence of clinically significant active infection, such as fever ≥ 38.0°C (100.5°F) at screening and through the time of the study drug administration on Study Day 0;
- Current allergy vaccination therapy (desensitization immunotherapy) with less than 3 months of stable maintenance doses prior to the baseline segmental allergen challenge. The allergy vaccination must not include desensitization to the allergen that will be used in the segmental allergen challenge;
- Receipt of any investigational drug therapy within 30 days or any biologic(s) within 5 half-lives of the agent prior to study drug administration through Study Day 126;
- Receipt of any therapy with a leukocyte-depleting agent (eg, rituximab, alemtuzumab) unless recovery in white cell count has been documented before screening;
- Pregnancy (sexually active females must have negative serum and urine pregnancy tests at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0);
- Is a nursing mother at the time of screening;
- Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A;
- History of significant systemic disease (eg, cancer, infection, hematological, renal, hepatic, coronary artery disease or other cardiovascular disease, endocrinologic, neurologic, rheumatologic, or gastrointestinal disease);
- History of cancer other than basal cell carcinoma or cervical carcinoma-in-situ treated with apparently successful curative therapy (remission for ≥ 1 year prior to screening);
- History of primary immunodeficiency;
- History of pancreatitis or currently active gastroduodenal ulcer;
- History of coagulation disorders or abnormal PT and PTT test results at screening;
- History of life-long urinary retention;
- History of use of tobacco products of more than one cigarette per month or equivalent within 1 year prior to screening or history of smoking of ≥ 10 pack-years;
- History of anaphylaxis;
- Elective surgery planned from the time of screening through Study Day 126;
- Clinically significant abnormalities (other than asthma) upon physical examination prior to study drug administration on Study Day 0;
- Clinically significant abnormality, as determined by the investigator, on 12-lead ECG or chest radiograph at the time of screening;
- At the time of screening, any of the following: hemoglobin, total white blood cell count (WBC), platelet count, sodium (Na), potassium (K), chloride (Cl), or carbon dioxide (CO2)out of the normal range; aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), amylase, lipase, or serum creatinine above the upper limits of normal (ULN); or other abnormal laboratory values in the screening panel that are judged by the principal investigator to be clinically significant; or
- No detectable levels of IL-9 in the Baseline Visit 2' BAL sample, or any finding upon physical examination or history of any disease that, in the opinion of the principal investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study.

No locations available

Arms	Assigned Interventions
Experimental: MEDI528 9 mg/kg MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion	Biological/Vaccine: MEDI528 9 mg/kg MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion
Placebo Comparator: PLACEBO Placebo administered as a single intravenous infusion	Other: PLACEBO Placebo administered as a single intravenous infusion

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 11 adult participants participated in the study between 19Jul2007 and 15Oct2008 at 2 sites in the United States of America.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Treatment assignments were determined using a block randomization procedure with a 1:1 ratio through an interactive voice response system. Only participants who had detectable levels of interleukin-9 in the Baseline Visit 2’ bronchioalveolar lavage sample will be randomized.

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Participant Flow: Overall Study

	PLACEBO	MEDI528 9 mg
STARTED	5	6
COMPLETED	5	5
NOT COMPLETED	0	1
ABNORMAL LAB DATA AT SCREENING	0	1

Baseline Characteristics

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

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Baseline Measures

	PLACEBO	MEDI528 9 mg	Total
Number of Participants [units: Participants]	5	6	11
Age Continuous [units: Years] Mean ± Standard Deviation	29.2 ± 7.8	22.3 ± 2.7	25.5 ± 6.4
Gender, Male/Female [units: Participants]
Male	2	5	7
Female	3	1	4

Outcome Measures

1. Primary Outcome Measure: Listing of Total Interleukin-9 (IL-9) Counts by Enzyme-linked Immunosorbent Assay in Bronchoalveolar Lavage Fluid (BAL) [ Time Frame: Baseline (2 to 4 weeks prior to Day 0) and Day 15 ]

Measure Type	Primary
Measure Name	Listing of Total Interleukin-9 (IL-9) Counts by Enzyme-linked Immunosorbent Assay in Bronchoalveolar Lavage Fluid (BAL)
Measure Description	The response of biologically active IL-9 in BAL fluid to the segmental allergen challenge, 1-2 days after the applying the allergen, prior to and 2 weeks after investigational product administration.
Time Frame	Baseline (2 to 4 weeks prior to Day 0) and Day 15
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.
All subjects who were randomized (n=11), received at least one dose of investigational product (MEDI-528 or placebo; n=10), and completed the 2-day BAL and segmental allergen challenge procedures at baseline (2-4 weeks prior to Day 0) and on Days 14 and 15 (n=2; 1 subject in each treatment group).

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	1	1
Listing of Total Interleukin-9 (IL-9) Counts by Enzyme-linked Immunosorbent Assay in Bronchoalveolar Lavage Fluid (BAL) [units: Picograms per milliliter]
Baseline	8.31	4.04
Day 15	40.05	43.01

No statistical analysis provided for Listing of Total Interleukin-9 (IL-9) Counts by Enzyme-linked Immunosorbent Assay in Bronchoalveolar Lavage Fluid (BAL)

2. Secondary Outcome Measure: Incidence of Adverse Events [ Time Frame: Days 0 - 126 ]

Measure Type	Secondary
Measure Name	Incidence of Adverse Events
Measure Description	Number of participants experiencing adverse events (includes both adverse events and serious adverse events)
Time Frame	Days 0 - 126
Safety Issue?	Yes

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.
All participants who were randomized (n=11) and received at least one dose of investigational product (MEDI-528 or placebo; n=10).

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Incidence of Adverse Events [units: Participants]	5	5

No statistical analysis provided for Incidence of Adverse Events

3. Secondary Outcome Measure: Incidence of Serious Adverse Events [ Time Frame: Days 0 - 126 ]

Measure Type	Secondary
Measure Name	Incidence of Serious Adverse Events
Measure Description	Number of participants experiencing serious adverse events
Time Frame	Days 0 - 126
Safety Issue?	Yes

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.
All participants who were randomized (n=11) and received at least one dose of investigational product (MEDI-528 or placebo; n=10).

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Incidence of Serious Adverse Events [units: Participants]	0	0

No statistical analysis provided for Incidence of Serious Adverse Events

4. Secondary Outcome Measure: Incidence of Anti-drug Antibodies (ADA) to MEDI-528 [ Time Frame: Days 0, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Incidence of Anti-drug Antibodies (ADA) to MEDI-528
Measure Description	Number of participants with ADA to MEDI-528
Time Frame	Days 0, 28, 56, 84, and 126
Safety Issue?	Yes

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.
All participants who were randomized (n=11) and received at least one dose of investigational product (MEDI-528 or placebo; n=10). One subject in the 9 mg/kg group had no sample collected on Day 126.

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Incidence of Anti-drug Antibodies (ADA) to MEDI-528 [units: Participants]	0	0

No statistical analysis provided for Incidence of Anti-drug Antibodies (ADA) to MEDI-528

5. Secondary Outcome Measure: Time to Peak Concentration (Tmax) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Time to Peak Concentration (Tmax)
Measure Description	Tmax of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Time to Peak Concentration (Tmax) [units: Day] Geometric Mean (Geometric Coefficient of Variation)		0.040 (88.4%)

No statistical analysis provided for Time to Peak Concentration (Tmax)

6. Secondary Outcome Measure: Peak Concentration (Cmax) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Peak Concentration (Cmax)
Measure Description	Cmax of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Peak Concentration (Cmax) [units: Microgram per milliliter] Geometric Mean (Geometric Coefficient of Variation)		210.634 (23.9%)

No statistical analysis provided for Peak Concentration (Cmax)

7. Secondary Outcome Measure: Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)] [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)]
Measure Description	AUC(0-t) of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)] [units: Microgram times day per milliliter] Geometric Mean (Geometric Coefficient of Variation)		4347.489 (24.1%)

No statistical analysis provided for Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)]

8. Secondary Outcome Measure: Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)]
Measure Description	AUC(0-infinity) of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] [units: Microgram times day per milliliter] Geometric Mean (Geometric Coefficient of Variation)		4845.344 (17.8%)

No statistical analysis provided for Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)]

9. Secondary Outcome Measure: Percent of Total Area Under the Concentration Curve Extrapolated from Last Measurable Time to Infinity [AUC(ext)] [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Percent of Total Area Under the Concentration Curve Extrapolated from Last Measurable Time to Infinity [AUC(ext)]
Measure Description	AUC(ext) of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Percent of Total Area Under the Concentration Curve Extrapolated from Last Measurable Time to Infinity [AUC(ext)] [units: Percentage of Total Area] Geometric Mean (Geometric Coefficient of Variation)		8.283 (78.8%)

No statistical analysis provided for Percent of Total Area Under the Concentration Curve Extrapolated from Last Measurable Time to Infinity [AUC(ext)]

10. Secondary Outcome Measure: Clearance (CL) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Clearance (CL)
Measure Description	CL of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Clearance (CL) [units: Milliliters per day] Geometric Mean (Geometric Coefficient of Variation)		167.702 (2.7%)

No statistical analysis provided for Clearance (CL)

11. Secondary Outcome Measure: Terminal Half-life (T1/2) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Terminal Half-life (T1/2)
Measure Description	T1/2 of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Terminal Half-life (T1/2) [units: Day] Geometric Mean (Geometric Coefficient of Variation)		32.134 (3.6%)

No statistical analysis provided for Terminal Half-life (T1/2)

12. Secondary Outcome Measure: Volume at Steady State (Vss) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Volume at Steady State (Vss)
Measure Description	Vss of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Volume at Steady State (Vss) [units: Milliliter] Geometric Mean (Geometric Coefficient of Variation)		7354.025 (5.6%)

No statistical analysis provided for Volume at Steady State (Vss)

13. Secondary Outcome Measure: Volume at Distribution (Vz) [ Time Frame: Days 0, 1, 7, 14, 15, 28, 56, 84, and 126 ]

Measure Type	Secondary
Measure Name	Volume at Distribution (Vz)
Measure Description	Vz of MEDI-528
Time Frame	Days 0, 1, 7, 14, 15, 28, 56, 84, and 126
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.
All participants who were randomized (n=11), received MEDI-528 (n=5), and had pharmacokinetic samples for analysis (n=4)

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg/kg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Measured Values

	PLACEBO	MEDI528 9 mg/kg
Number of Participants Analyzed [units:participants]	0	4
Volume at Distribution (Vz) [units: Milliliter] Geometric Mean (Geometric Coefficient of Variation)		7772.894 (3.5%)

No statistical analysis provided for Volume at Distribution (Vz)

Serious Adverse Events

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

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion

Serious Adverse Events

	PLACEBO	MEDI528 9 mg
Total, serious adverse events
# participants affected / at risk	0/5 (0.00%)	0/5 (0.00%)

Other Adverse Events

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

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
PLACEBO	Placebo administered as a single intravenous dose
MEDI528 9 mg	MEDI-528 at a dose of 9 mg/kg administered as a single intravenous infusion