Evaluation Of Safety, Tolerability And Pharmacokinetics Of Single And Multiple Doses Of PF-06730512

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety, tolerability and pharmacokinetics of escalating single and multiple intravenous (IV) infusions and subcutaneous (SC) injections of PF-06730512 in healthy subjects.

Official Title
-----------------
A Phase 1, Randomized, Double Blind, Sponsor-open, Placebo-controlled, First-in-human Trial To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf-06730512 After Single And Multiple Ascending Intravenous Infusion Or Subcutaneous Administration To Healthy Adult Subjects And An Open-label Evaluation In Healthy Japanese Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Biological: PF-06730512
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12-lead electrocardiogram (ECG), or clinical laboratory tests. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Exclusion Criteria: - History of allergic reactions to diagnostic or therapeutic protein. History of recurrent infections or active infection within 28 days of screening. Exposure to live vaccines within 28 days of screening. - History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb). As an exception, a positive hepatitis B surface antibody (HBsAb) finding as a result of subject vaccination is permissible.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06730512<br>Study Drug being used in the study | Biological: PF-06730512<br>* Comparison of different dosages of PF-06730512 to Placebo<br>|
| Placebo Comparator: Placebo<br>Placebo for IV/SC administration | Drug: Placebo<br>* Comparison of Placebo to different doses of PF-06730512<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment Emergent Treatment-Related Adverse Event(s) | Number of Subjects With Treatment Emergent Treatment-Related Adverse Event(s) | Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Number of subjects with injection site reaction(s) | Number of subjects with injection site reaction(s) | Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Number of subjects with laboratory test findings of potential clinical importance | Number of subjects with laboratory test findings of potential clinical importance | Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Number of subjects with vital signs findings of potential clinical importance | Number of subjects with vital signs findings of potential clinical importance | Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Number of subjects with ECG findings of potential clinical importance | Number of subjects with ECG findings of potential clinical importance | Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of PF-06730512 | Maximum Observed Plasma Concentration (Cmax) of PF-06730512 | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Time to Reach Maximum Observed Concentration (Tmax) of PF-06730512 | Time to Reach Maximum Observed Concentration (Tmax) of PF-06730512 | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06730512 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06730512 | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] of PF-06730512, as permitted | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] of PF-06730512, as permitted | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Clearance (CL) or Apparent Clearance (CL/F) of PF-06730512, as permitted | Clearance (CL) or Apparent Clearance (CL/F) of PF-06730512, as permitted | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06730512 | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06730512 | Day 1 to approximately Day 113 | 
| Apparent Volume of Distribution of PF-06730512, as permitted | Apparent Volume of Distribution of PF-06730512, as permitted | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Terminal half-life, as permitted | Terminal half-life, as permitted | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) | 
| Accumulation ratio (Rac), as permitted | Accumulation ratio (Rac), as permitted | Day 1 to approximately Day 113 | 
| Minimum observed concentration during the dosing interval (Cmin) | Minimum observed concentration during the dosing interval (Cmin) | Day 1 to approximately Day 113 | 
| Incidence of the development of anti-drug antibody (ADA) and neutralizing antibody (NAb) | Incidence of the development of anti-drug antibody (ADA) and neutralizing antibody (NAb) | Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose) |