A Multiple Dose Study Of PF-05161704 In Healthy Volunteers

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of multiple escalating oral doses of PF-05161704 in healthy volunteers

Official Title
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A Phase 1 Placebo-Controlled Study To Assess The Safety, Tolerability And Pharmacokinetics Of Pf-05161704 After Administration Of Multiple Escalating Oral Doses In Healthy Volunteers

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo
* Drug: PF-05161704 or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female (non-childbearing potential) subjects between the ages of 18 and 55 years, inclusive Body Mass Index (BMI) of 24.5 to 35.5 kg/m2 and a total body weight >50 kg (110 lbs.) Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Any condition possibly affecting drug absorption (e.g., gastrectomy). History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening. History or evidence of habitual use of tobacco or nicotine containing products within 3 months of screening or positive cotinine test at screening or Day -1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Experimental: 5 mg PF-05161704 or Placebo<br> | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered twice daily for 14 days immediately after breakfast and dinner<br>|
| Experimental: 15 mg PF-05161704 or Placebo<br>Planned dose: may be modified based on emerging PK and safety data. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered twice daily for 14 days immediately after breakfast and dinner<br>|
| Experimental: 50 mg PF-05161704 or Placebo<br>Planned dose: may be modified based on emerging PK and safety data. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered twice daily for 14 days immediately after breakfast and dinner<br>|
| Experimental: 150 mg PF-05161704 or Placebo<br>Planned dose: may be modified based on emerging PK and safety data. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered twice daily for 14 days immediately after breakfast and dinner<br>|
| Experimental: xx mg PF-05161704 or Placebo<br>Planned dose and dosing regimen will be determined based on emerging PK and safety data. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered twice daily for 14 days immediately after breakfast and dinner or once daily for 14 days immediately after breakfast<br>|
| Experimental: xxx mg PF-05161704 or Placebo<br>Dose will be determined based on data from previous 5 arms. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered once daily for 14 days immediately after breakfast<br>|
| Experimental: yy mg PF-05161704 or Placebo<br>Dose will be determined based on data from previous 6 arms | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered once daily for 14 days immediately after breakfast<br>|
| Experimental: yyy mg PF-05161704 or Placebo<br>Dose will be determined based on data from previous 7 arms. | Drug: PF-05161704 or Placebo<br>* PF-05161704 and Placebo (3:1) oral dosing Suspensions administered once daily for 14 days immediately after breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability endpoints evaluated by adverse event monitoring, laboratory values, cardiovascular monitoring |  | 2 weeks | 
| Pharmacokinetic Endpoints: single dose and steady state pharmacokinetics of PF-05161704 and its metabolite PF-05200145. Urinary recovery will also be assessed for PF-05161704 and PF-05200145 |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic Endpoints: Absolute value and change from Day 0 baseline in postprandial GLP-1. Postprandial plasma PYY, triglycerides and apoB48. Absolute value and change from baseline in apoB100 and VLDL |  | 2 weeks | 
| Exploratory Parameters: absolute value and change from Day 0 baseline in concentrations of fasting serum lipids and body weight |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Ascending Dose, Phase 1, Safety and Tolerability, PK, Healthy Subjects