Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single-Dose Subcutaneous Administration of MEDI-528

Study identifier:MI-CP109

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single-Dose Subcutaneous Administration of MEDI-528, a Humanized Monoclonal Anti-Interleukin-9 Antibody, in Healthy Adult Volunteers

Medical condition

Healthy

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

19 Years - 49 Years

Date

Study Start Date: 01 Jun 2005

Primary Completion Date: 01 Apr 2006

Study Completion Date: 01 Jul 2006

Study design

Allocation: Non-randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2013 by MedImmune

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Males and females age 19 up to, and including, 49 years of age at the time of the first dose of study drug
- Weight less than 89 kg
- Written informed consent obtained from the volunteer
- Healthy by medical history and physical examination
- Sexually active females, unless surgically sterile or at least two years post-menopausal or an FSH≥40 mIu/mL, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 3 months before the first dose of study drug, and must agree to continue using such precautions through the study period of 84 days. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions through Study Day 84 after their dose of study drug.
- Use of common over-the-counter medications such as topical corticosteroids, decongestants, antihistamines, analgesics, and antacids is permitted unless, in the opinion of the investigator, it would interfere with either the volunteer's ability to complete the study or interpretation of the study results.
- Ability to complete the follow-up period of 84 days
- Willing to forego other forms of experimental treatment during the study period of 84 days
- Willing to forego vigorous activity 1 - 2 days before dosing, and before each study visit.

Exclusion Criteria

- Acute illnesses or evidence of significant active infection, such as fever greater than or equal to 38.0 C (100.5°F) at the start of the study
- Use of prescription medications, other than oral contraceptives, in the 28-day period before Study Day 0
- Any blood donation or significant loss of blood within 6 months of time of entry into the study
- History of immunodeficiency or receipt of immunosuppressive drugs
- History of allergy or reaction to any component of the MEDI-528 formulation
- History of substance abuse that, in the opinion of the investigator, may compromise the ability of the study subject to complete the study and follow-up period
- Evidence of any systemic disease, neurologic abnormality, lymphadenopathy, or splenomegaly upon physical examination
- Evidence of infection with hepatitis A, B, or C virus or HIV-1
- Receipt of immunoglobulins or blood products within 60 days of entering the study
- Receipt of any investigational drug therapy or standard vaccine therapy, other than vaccination for influenza, within 60 days of the first dose of study drug through Study Day 84 (use of licensed agents for indications not listed in the package insert is permitted)
- Receipt of MEDI-528 in any previous clinical study
- At Screening (must be within 21 days before study dose administration) any of the following: Hgb, total WBC, platelet count, Na, K, C1, CO2, AST, ALT, BUN, glucose, amylase, lipase, creatinine, or troponin out of the normal range; other abnormal laboratory values in the screening panel that, in the opinion of the principal investigator, are judged to be clinically significant
- Clinically significant abnormality, as determined by the investigator, on 12-lead electrocardiogram at the time of initial screening
- Clinically significant abnormalities noted on baseline brain MRI
- Elective surgery planned during the study period through Study Day 84
- Pregnancy (sexually active females must have a negative serum pregnancy test on the day of the first dose of study drug, before dosing)
- Nursing mother
- The presence of any condition or concern which, in the opinion of the investigator, may interfere with the conduct or interpretation of the study.

Location

MDS Pharma Services

New Orleans, LA, United States, 70119

Location

MDS Pharma Services

Lincoln, NE, United States, 68502

Arms	Assigned Interventions
Experimental: MEDI-528 0.3 mg/kg MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose	Biological/Vaccine: MEDI-528 0.3 mg/kg MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
Experimental: MEDI-528 1 mg/kg MEDI-528 (1 mg/kg) administered as a single, SC dose	Biological/Vaccine: MEDI-528 1 mg/kg MEDI-528 (1 mg/kg) administered as a single, SC dose
Experimental: MEDI-528 3 mg/kg MEDI-528 (3 mg/kg) administered as a single, SC dose	Biological/Vaccine: MEDI-528 3 mg/kg MEDI-528 (3 mg/kg) administered as a single, SC dose
Experimental: MEDI-528 9 mg/kg MEDI-528 (9 mg/kg) administered as a single, SC dose	Biological/Vaccine: MEDI-528 9 mg/kg MEDI-528 (9 mg/kg) administered as a single, SC dose

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 29 participants provided written informed consent and participated in the study at 2 sites in the United States of America between 10Jun2005 and 18Apr2006.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants received MEDI-528 in an open-label manner.

Reporting Groups

	Description
MEDI-528 0.3 mg
MEDI-528 1 mg
MEDI-528 3 mg
MEDI-528 9 mg

Participant Flow: Overall Study

	MEDI-528 0.3 mg	MEDI-528 1 mg	MEDI-528 3 mg	MEDI-528 9 mg
STARTED	6	11	6	6
COMPLETED	0	6	6	6
NOT COMPLETED	6	5	0	0
Lost to Follow-up	6	5	0	0

Baseline Characteristics

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

Reporting Groups

	Description
MEDI-528 0.3 mg
MEDI-528 1 mg
MEDI-528 3 mg
MEDI-528 9 mg

Baseline Measures

	MEDI-528 0.3 mg	MEDI-528 1 mg	MEDI-528 3 mg	MEDI-528 9 mg	Total
Number of Participants [units: Participants]	6	11	6	6	29
Age Continuous [units: Years] Mean ± Standard Deviation	27.2 ± 8.7	25.2 ± 9.7	34.7 ± 7.8	33.2 ± 13.9	29.2 ± 10.5
Gender, Male/Female [units: Participants]
Male	2	7	3	3	15
Female	4	4	3	3	14

Outcome Measures

1. Primary Outcome Measure: Incidence of Adverse Events [ Time Frame: Days 0 - 84 ]

Measure Type	Primary
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 - 84
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 subjects who received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	6	6	6	6
Incidence of Adverse Events [units: Participants]	5	4	6	6

No statistical analysis provided for Incidence of Adverse Events

2. Primary Outcome Measure: Incidence of Abnormal Troponin Levels [ Time Frame: Days 0, 1, 7, 14, and 28 ]

Measure Type	Primary
Measure Name	Incidence of Abnormal Troponin Levels
Measure Description	Number of participants with troponin levels greater than upper limit of normal
Time Frame	Days 0, 1, 7, 14, and 28
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 subjects who received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	6	6	6	6
Incidence of Abnormal Troponin Levels [units: Participants]	0	0	0	0

No statistical analysis provided for Incidence of Abnormal Troponin Levels

3. Primary Outcome Measure: Incidence of Clinically Significant Changes from Baseline in Neurologic Exam [ Time Frame: Days 0, 7, 14, 21, 28, 42, and 84 ]

Measure Type	Primary
Measure Name	Incidence of Clinically Significant Changes from Baseline in Neurologic Exam
Measure Description	Number of participants with clinically significant changes from baseline in neurologic exam
Time Frame	Days 0, 7, 14, 21, 28, 42, and 84
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 subjects who received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	6	6	6	6
Incidence of Clinically Significant Changes from Baseline in Neurologic Exam [units: Participants]	0	0	0	0

No statistical analysis provided for Incidence of Clinically Significant Changes from Baseline in Neurologic Exam

4. Primary Outcome Measure: Incidence of Changes from Baseline in the Day 28 Magnetic Resonance Imaging (MRI) of the Brain [ Time Frame: Days 0 and 28 ]

Measure Type	Primary
Measure Name	Incidence of Changes from Baseline in the Day 28 Magnetic Resonance Imaging (MRI) of the Brain
Measure Description	Number of participants with changes from baseline in the Day 28 MRI of the brain
Time Frame	Days 0 and 28
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 subjects who received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	6	6	6	6
Incidence of Changes from Baseline in the Day 28 Magnetic Resonance Imaging (MRI) of the Brain [units: Participants]	0	1	1	1

No statistical analysis provided for Incidence of Changes from Baseline in the Day 28 Magnetic Resonance Imaging (MRI) of the Brain

5. Primary Outcome Measure: Incidence of Serious Adverse Events [ Time Frame: Days 0 - 84 ]

Measure Type	Primary
Measure Name	Incidence of Serious Adverse Events
Measure Description	Number of participants experiencing serious adverse events
Time Frame	Days 0 - 84
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 subjects who received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	6	6	6	6
Incidence of Serious Adverse Events [units: Participants]	0	0	0	0

No statistical analysis provided for Incidence of Serious Adverse Events

6. Secondary Outcome Measure: Incidence of Anti-drug Antibodies (ADA) to MEDI-528 [ Time Frame: Days 0, 14, 28, 42, and 84 ]

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, 14, 28, 42, and 84
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 subjects who received MEDI-528 (no safety or ADA information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Partial ADA information was available in the 0.3 mg/kg group (Day 0 and 14, n=5; Day 28, n=2; Day 42 and 84, n = 0)

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	5	6	6	6
Incidence of Anti-drug Antibodies (ADA) to MEDI-528 [units: Participants]	0	0	0	0

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

7. Secondary Outcome Measure: Time to Observed Maximum Serum Concentration (Tmax) [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Time to Observed Maximum Serum Concentration (Tmax)
Measure Description	Tmax of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	4	6	6	6
Time to Observed Maximum Serum Concentration (Tmax) [units: Days] Mean (Standard Deviation)	5.51 (1.90)	4.17 (1.60)	4.50 (1.52)	5.00 (1.90)

No statistical analysis provided for Time to Observed Maximum Serum Concentration (Tmax)

8. Secondary Outcome Measure: Observed Maximum Serum Concentration (Cmax) [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Observed Maximum Serum Concentration (Cmax)
Measure Description	Cmax of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	4	6	6	6
Observed Maximum Serum Concentration (Cmax) [units: Micrograms per milliliter] Mean (Standard Deviation)	2.83 (0.73)	14.48 (6.68)	23.00 (5.62)	82.50 (19.64)

No statistical analysis provided for Observed Maximum Serum Concentration (Cmax)

9. Secondary Outcome Measure: Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)] [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

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, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	4	6	6	6
Area Under the Concentration Curve from Time Zero to Last Measurable Concentration [AUC(0-t)] [units: Micrograms times day per milliliter] Mean (Standard Deviation)	18.47 (10.26)	329.7 (113.72)	923.27 (226.71)	3053.34 (908.30)

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

10. Secondary Outcome Measure: Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] of MEDI-528 [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] of MEDI-528
Measure Description	AUC(0-infinity) of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	2	6	6	6
Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] of MEDI-528 [units: Microgram times day per milliliter] Mean (Standard Deviation)	40.78 (0.34)	667.68 (201.99)	1287.31 (413.92)	3770.06 (1396.66)

No statistical analysis provided for Area Under the Concentration Curve from Time Zero to Infinity [AUC(0-infinity)] of MEDI-528

11. 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, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

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, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	2	6	6	6
Percent of Total Area Under the Concentration Curve Extrapolated from Last Measurable Time to Infinity [AUC(ext)] [units: Percent] Mean (Standard Deviation)	33.32 (6.26)	50.90 (13.82)	26.05 (9.16)	16.61 (8.97)

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

12. Secondary Outcome Measure: Total Body Clearance (CL) [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Total Body Clearance (CL)
Measure Description	CL of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	2	6	6	6
Total Body Clearance (CL) [units: Liter per day] Mean (Standard Deviation)	0.49 (0.00)	0.12 (0.05)	0.19 (0.10)	0.20 (0.09)

No statistical analysis provided for Total Body Clearance (CL)

13. Secondary Outcome Measure: Half-life (T1/2) [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Half-life (T1/2)
Measure Description	T1/2 of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	2	6	6	6
Half-life (T1/2) [units: Days] Mean (Standard Deviation)	6.47 (0.85)	86.85 (19.86)	44.43 (11.48)	33.44 (11.32)

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

14. Secondary Outcome Measure: Apparent Extravascular Terminal Phase Volume of Distribution (Vz/F) [ Time Frame: Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84 ]

Measure Type	Secondary
Measure Name	Apparent Extravascular Terminal Phase Volume of Distribution (Vz/F)
Measure Description	Vz/F of MEDI-528
Time Frame	Days 0, 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 42, and 84
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 received MEDI-528 (no safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina). Two subjects in the 0.3 mg/kg group had no blood samples for pharmacokinetic analysis.

Reporting Groups

	Description
MEDI-528 0.3 mg/kg	MEDI-528 (0.3 mg/kg) administered as a single, subcutaneous (SC) dose
MEDI-528 1 mg/kg	MEDI-528 (1 mg/kg) administered as a single, SC dose
MEDI-528 3 mg/kg	MEDI-528 (3 mg/kg) administered as a single, SC dose
MEDI-528 9 mg/kg	MEDI-528 (9 mg/kg) administered as a single, SC dose

Measured Values

	MEDI-528 0.3 mg/kg	MEDI-528 1 mg/kg	MEDI-528 3 mg/kg	MEDI-528 9 mg/kg
Number of Participants Analyzed [units:participants]	2	6	6	6
Apparent Extravascular Terminal Phase Volume of Distribution (Vz/F) [units: Liters] Mean (Standard Deviation)	4.58 (0.64)	14.57 (8.61)	10.91 (1.21)	8.65 (1.40)

No statistical analysis provided for Apparent Extravascular Terminal Phase Volume of Distribution (Vz/F)

Serious Adverse Events

Time Frame	Days 0-84
Additional Description	No safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina.

Reporting Groups

	Description
MEDI-528 0.3 mg	No text entered.
MEDI-528 1 mg	No text entered.
MEDI-528 3 mg	No text entered.
MEDI-528 9 mg	No text entered.

Serious Adverse Events

	MEDI-528 0.3 mg	MEDI-528 1 mg	MEDI-528 3 mg	MEDI-528 9 mg
Total, serious adverse events
# participants affected / at risk	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)

Other Adverse Events

Time Frame	Days 0-84
Additional Description	No safety information was available for 5 subjects in the 1.0 mg/kg group due to Hurricane Katrina.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
MEDI-528 0.3 mg	No text entered.
MEDI-528 1 mg	No text entered.
MEDI-528 3 mg	No text entered.
MEDI-528 9 mg	No text entered.

Other Adverse Events

MEDI-528 0.3 mg

MEDI-528 1 mg

MEDI-528 3 mg

MEDI-528 9 mg

Total, other (not including serious) adverse events

# participants affected / at risk

5/6 (83.33%)

4/6 (66.67%)

6/6 (100.00%)

Ear and labyrinth disorders

Ear pain¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

General disorders and administration site conditions

Injection site bruising¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

# events

General disorders and administration site conditions

Injection site pain¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Infections and infestations

Ear infection¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Injury, poisoning and procedural complications

Cartilage injury¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Investigations

Blood bicarbonate decreased¹,^†

# participants affected / at risk

2/6 (33.33%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Investigations

Blood chloride increased¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

# events

Investigations

Blood glucose increased¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

2/6 (33.33%)

# events

Investigations

Blood sodium decreased¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Investigations

Blood urea increased¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Investigations

Lymph node palpable¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

2/6 (33.33%)

# events

Investigations

Protein urine present¹,^†

# participants affected / at risk

3/6 (50.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Investigations

Red blood cells urine positive¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

# events

Investigations

White blood cell count increased¹,^†

# participants affected / at risk

1/6 (16.67%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

2/6 (33.33%)

# events

Nervous system disorders

Sinus headache¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

# events

Reproductive system and breast disorders

Breast tenderness¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Reproductive system and breast disorders

Dysmenorrhoea¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Reproductive system and breast disorders

Haematospermia¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Reproductive system and breast disorders

Menorrhagia¹,^†

# participants affected / at risk

0/6 (0.00%)

3/6 (50.00%)

0/6 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

1/6 (16.67%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

4/6 (66.67%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Sinus congestion¹,^†

# participants affected / at risk

0/6 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Throat irritation¹,^†

# participants affected / at risk

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 9.0

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
No text entered.

Results Point of Contact

Name/Title:	Don Raible, MD
Organization:	MedImmune
Phone	301-398-0000
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

Amy Evangelista

301-398-4033

evangelistaa@medimmune.com

Investigators

Principal Investigator

Barbara White

MedImmune, Inc

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

MDS Pharma Services

MDS Pharma Services

Trial Results Summaries