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

Study Overview
=================
Brief Summary
-----------------
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
-----------------
A Phase 1 Placebo-Controlled Study To Assess Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 Administered In A Tablet Formulation In Otherwise Healthy Overweight And Obese Subjects

Conditions
-----------------
Diabetes Mellitus Type 2

Intervention / Treatment
-----------------
* Drug: PF-05175157
* Drug: Midazolam
* Other: Placebo
* Drug: Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 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). Women must be of non childbearing potential. Body Mass Index (BMI) of 25 to 35 kg/m2 inclusive; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject. 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
-----------------
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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-05175157, Midazolam<br>Day 0: Midazolam 2 mg administered alone Days 1-14: 200 mg PF-05175157 administered BID Day 11: Midazolam and PF-05175157 | Drug: PF-05175157<br>* 200 mg tablet administered twice per day for 14 days<br>Drug: Midazolam<br>* 2mg administered as single doses on Days 0 and 11<br>|
| Experimental: Placebo, Midazolam<br>Day 0: Midazolam 2 mg administered alone Days 1-14: Placebo administered BID Day 11: Midazolam and Placebo | Other: Placebo<br>* Placebo administered twice per day for 14 days<br>Drug: Midazolam<br>* 2mg administered as single doses on Days 0 and 11<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma PF-05175157 Concentration (Cmax) | Single Dose | 0 - 10 hrs postdose | 
| Area Under the Curve from Time Zero to end of dosing interval for PF-05175157 (AUCtau) | Single Dose | 0 - 10 hrs postdose | 
| Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax) | Single Dose | 0 - 10 hrs postdose | 
| Maximum Observed Plasma PF-05175157 Concentration (Cmax) | Steady State | 0 - 48 hours postdose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) for PF-05175157 | Steady State | 0 - 48 hours postdose | 
| Time to Reach Maximum Observed Plasma PF-05175157 Concentration (Tmax) | Steady State | 0 - 48 hours postdose | 
| Apparent Oral Clearance of PF-05175157 (CL/F) |  | 0 - 48 hours postdose | 
| Accumulation Ratio of PF-05175157 (Rac) |  | 0 - 10 hours postdose | 
| Plasma Decay Half-Life of PF-05175157 (t1/2) |  | 0 - 48 hours postdose | 
| Apparent Volume of Distribution of PF-05175157 (Vz/F) |  | 0 - 48 hours postdose | 
| Urinary Recovery for PF-05175157 (AE24) | Amount of PF-05175157 recovered in urine over 24 hours | 0 - 24 hours postdose | 
| Renal Clearance for PF-05175157 (CLr) |  | 0 - 24 hours post dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration for midazolam [AUC (0-t)] |  | 0 - 48 hours postdose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time for midazolam [AUC (0 - inf)] |  | 0 - 48 hours postdose | 
| Maximum Observed Plasma Concentration for midazolam (Cmax) |  | 0 - 48 hours postdose | 
| Time to Reach Maximum Observed Plasma midazolam Concentration (Tmax) |  | 0 - 48 hours post dose | 
| Plasma Decay Half-Life of midazolam (t1/2) |  | 0 - 48 hours postdose | 
| Fasting triglycerides |  | 14 days | 
| Total cholesterol |  | 14 days | 
| LDL cholesterol |  | 14 days | 
| HDL cholesterol |  | 14 days |