A Phase 1 Study To Evaluate The Safety And Tolerability Of PF-06252616 In Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine if the study drug, PF-06252616 is safe and well tolerated when given to adult healthy volunteers.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PF-06252616 In Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Biological: PF-06252616
* Drug: Placebo
* Biological: PF-06252616
* Drug: Placebo
* Biological: PF-06252161
* Drug: Placebo
* Biological: PF-06252616
* Drug: Placebo
* Biological: PF-06252616
* Drug: Placebo
* Biological: PF-06252616
* Drug: Placebo
* Biological: PF-06252616
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single Dose Cohorts-Healthy male and/or female non-child bearing subjects between the ages of 18 and 55 years, inclusive. Repeat Dose Cohort-Healthy male and/or female non-child bearing subjects between the ages of 18 and less than 65 years, inclusive. Exclusion Criteria: Presence or history of muscle disease (eg, polymyositis or rhabdomyolysis). Weight loss or gain of >5% within 30 days of Screening, as reported by subject. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, immunologic, metabolic urologic, dermatologic, renal, allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) and any other major disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Biological: PF-06252616<br>* 1.0 milligram per kilogram of PF-06252616, IV infusion, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, single dose<br>|
| Placebo Comparator: 2<br> | Biological: PF-06252616<br>* 3.0 milligram per kilogram of PF-06252616, IV infusion, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, single dose<br>|
| Placebo Comparator: 3<br> | Biological: PF-06252161<br>* 10.0 milligram per kilogram of PF-06252616, IV infusion, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, single dose<br>|
| Placebo Comparator: 4<br> | Biological: PF-06252616<br>* 3.0 milligram per kilogram of PF-06252616, Subcutaneous injection, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, Subcutaneous injection, single dose<br>|
| Placebo Comparator: 5<br>Repeat dose of PF-06252616, IV infusion, single dose - 10.0 miligram per kilogram | Biological: PF-06252616<br>* 10.0 miligram per kilogram of PF-06252616, IV infusion, repeat dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, repeat dose<br>|
| Placebo Comparator: 6<br> | Biological: PF-06252616<br>* 20.0 milligram per kilogram of PF-06252616, IV infusion, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, single dose<br>|
| Placebo Comparator: 7<br> | Biological: PF-06252616<br>* 40.0 milligram per kilogram of PF-06252616, IV infusion, single dose<br>Drug: Placebo<br>* Placebo for PF-06252616, IV infusion, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment related Adverse Events. |  | Day 197 | 
| Severity of treatment related Adverse Events. |  | Day 197 | 
| Incidence of abnormal lab findings. |  | Day 197 | 
| Magnitude of abnormal lab findings. |  | Day 197 | 
| Abnormal and clinically relevant changes in Blood Pressure. |  | Day 197 | 
| Abnormal and clinically relevant changes in Pulse Rate. |  | Day 197 | 
| Abnormal and clinically relevant changes in Respiratory Rate. |  | Day 197 | 
| Abnormal and clinically relevant changes in temperature. |  | Day 197 | 
| Abnormal and clinically relevant changes in ECG parameters. |  | Day 197 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PF-06252616 concentration in serum as measured by a validated PK assay for Cmax (maximum concentration) |  | Through Day 197 post dosing | 
| Pharmacodynamic activity as measured by serum concentrations of GDF-8 (myostatin) as measured by a GDF-8 assay |  | Through Day 197 post dosing | 
| Incidence of development of anti-drug antibody (ADA) as measured by an ADA assay |  | Through Day 197 post dosing | 
| Pharmacologic activity as measured by the percent change in lean body mass as measured by DXA |  | Through Day 113 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for Tmax (time to reach maximum concentration) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for AUCinf (area under the curve serum concentration-time profile from time zero to infinity |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for AUClast (area under the curve serum concentration from time zero to the time of the last quantifiable concentration) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for t1/2 (half-life time for the serum concentration to decrease by half). |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for AUCτ (area under the curve serum concentration by dose interval) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for MRT (mean residence time) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for CL (rate of clearance from serum) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for CLss (rate of steady state clearance from serum in the repeat dose cohort) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for Vz /F(volume of distribution is the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug.) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for Vss(volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug. |  | Through Day 197 post dosing | 
| Steady state volume of distribution is the apparent volume of distribution at steady-state.) |  | Through Day 197 post dosing | 
| PF-06252616 concentration in serum as measured by a validated PK assay for RAC (accumulation ratio for AUC) |  | Through Day 197 post dosing |