Multiple Dose Safety Toelrability, Pharmacokinetics and Midazolam Interaction In Healthy Overweight And Obese Subjects

Study Overview
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Brief Summary
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This study is designed to assess the safety, tolerability and pharmacokinetics of multiple oral 200-mg doses of Pf-05175157 administered twice daily for 14 days in healthy overweight and obese subjects.

Official Title
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A Phase 1 Placebo-Controlled Study To Assess The Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 In Otherwise Healthy Overweight And Obese Subjects

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders

Intervention / Treatment
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* Drug: Pf-05175157
* Drug: placebo
* Drug: midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects 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 and pulse rate measurement, 12 lead ECG and clinical laboratory tests). Body Mass Index (BMI) of 25 to 35 kg/m2 inclusive; and a total body weight >50 kg (110 lbs). Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 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). Evidence or history of any chronic ongoing or current pulmonary disease. History of smoking in the past 5 years and a history of smoking more than 10 pack years, or history or evidence of habitual use of other (non smoked) tobacco or nicotine containing products. Active ocular disease including infection, glaucoma, seasonal allergies, dry eye symptoms or retinal/optic nerve disease.

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
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm Label Pf-05175157, placebo, midazolam<br> | Drug: Pf-05175157<br>* 200-mg administered twice daily for 14 days<br>Drug: placebo<br>* placebo administered twice daily for 14 days<br>Drug: midazolam<br>* midazolam 3-mg admistered as single doses on Day 0 and Day 11.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hrs postdose | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Plasma Decay Half-Life (t1/2) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Apparent Volume of Distribution (Vz/F) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Apparent Oral Clearance (CL/F) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours postdose | 
| Accumulation Ratio (Rac) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose | 
| Ae,tau |  | 0-12 hr | 
| Ae% |  | 0-12 hr | 
| Clr |  | 0-12 hr | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours | 
| Plasma Decay Half-Life (t1/2) |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] |  | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours | 
| fasting triglycerides |  | 14 days | 
| fasting LDL-cholesterol |  | 14 days | 
| fasting total cholesterol |  | 14 days | 
| fasting HDL cholesterol |  | 14 days |