Multiple Dose Study Of PF-05231023 In Obese Adult Subjects

Study Overview
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Brief Summary
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This is a trial in obese subjects to study the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of PF-05231023.

Official Title
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A Phase 1, Placebo-Controlled, Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenous Doses Of PF-05231023 In Obese Adult Subjects

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Other: Placebo
* Drug: 100 mg PF-05231023


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects of non-childbearing potential between the ages of 21 and 70. Subjects with a BMI of 30 to 45.4 kg/m2 and total body weight >110 lbs. Exclusion Criteria: Recent (6 months) unstable concurrent disease. History of allergic disease or drug allergies. Any condition affecting food consumption or absorption.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 0.9% w/v sodium chloride injection, United States Pharmacopeia (USP), twice a week for 4 weeks.<br>|
| Experimental: 100 mg PF-05231023<br> | Drug: 100 mg PF-05231023<br>* 100 mg IV infusion twice a week for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were also reported for the 7-day pre-randomization period. | Day -7 through the last follow-up (Day 68) | 
| Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern | Vital signs included supine systolic blood pressure, diastolic blood pressure and pulse rate. Vital signs criteria of potential clinical concern were 1), blood pressure: systolic greater than or equal to (>=)30 millimeters of mercury (mm Hg) change from baseline in the same posture or systolic less than (<)90 mm Hg; diastolic >=20 mm Hg change from baseline in the same posture or diastolic <50 mm Hg; 2), Pulse rate: supine/Sitting: <40 or greater than (>) 120 beats per minute (bpm); Standing: <40 or >140 bpm. | Days -7 up to the last follow-up (Day 68) | 
| Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern | ECG criteria of potential clinical concern were 1), PR interval:>=300 msec, >=25% increase when baseline >200 msec, or >=50% increase when baseline <=200 msec; 2), QRS interval:>=140 msec, or >=50% increase from baseline; 3), QT interval corrected for heart rate (QTc)/QTc interval using Fridericia's formula (QTcF):>=500 msec, QTcF interval: absolute value >=450 - <480 msec(borderline), >=480 msec (prolonged), absolute change 30 - <60 msec (borderline) or >=60 msec (prolonged). 12-lead ECG (triplicate) was performed on Day 0 and 12-lead ECG (singlet) was performed at other times. | Days -7 up to the last follow-up (Day 68) | 
| Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies. | Anti-PF-05231023 antibodies were analyzed using a tiered testing strategy of screen, confirm, and titer characterization. Positive was defined as titer value >=6.23 and negative was defined as titer value <6.23. Samples tested positive were also to be analyzed in a neutralization assay to determine whether or not they were neutralizing or non-neutralizing. | Days 1 up to the last follow-up (Day 68) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Abnormal Clinical Laboratory Measurements | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. | Days -7 up to the last follow-up (Day 68) | 
| Area Under the Concentration Versus Time Curve From Time 0 to Tau, the Dosing Interval (AUCtau) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Days 1 and 25 | 
| Maximum Plasma Concentration (Cmax) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Days 1 and 25 | 
| Lowest Concentration Observed During Dosing Interval (Cmin) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 
| Average Concentration at Steady State (Cav) of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 
| Time for Cmax (Tmax)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 
| Clearance (CL)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 
| Terminal Elimination Half-life (t1/2)of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 
| Observed Accumulation Ratio (Rac) for Cmax and AUCtau of PF-05231023 (C-terminus and N-terminus PF-05231023 and Total CVX-2000 Antibody Scaffold) |  | Day 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T2DM, obesity, safety, multiple dose, intravenous