A Single Dose Study In Japanese And Western Healthy Subjects To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-04991532

A Phase 1, Randomized, Double Blind, Placebo-Controlled, Single Dose Escalation Study In Japanese Healthy Subjects, And Open Label, Single Dose Study In Western Healthy Subjects To Investigate The Safety, Tolerability, And Pharmacokinetics of PF-04991532.

This study is to investigate the safety, tolerability and pharmacokinetics of single ascending oral doses of PF-04991532 in Japanese healthy subjects. The secondary objective is to investigate the pharmacokinetics and safety of single ascending oral doses of PF-04991532 in Western healthy subjects and to compare the pharmacokinetics between Japanese and Western healthy subjects.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Intervention / Treatment: Drug: PF-04991532; Drug: Placebo; Drug: PF-04991532

Detailed Description

Safety/Tolerability and Pharmacokinetics

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects of non-childbearing potential, 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 17.5 to 30.5 kg/m2; and a total body weight > 50 kg (110 lbs).
• Japanese subjects must have four Japanese grandparents who were born in Japan.
• Mean body weight and the body weight range of Western subjects must be within ±10% of the Japanese subjects.

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).
• Screening supine blood pressure >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest.
• Any condition possibly affecting drug absorption (eg, 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.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
• 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
• Pregnant or nursing females or women of childbearing potential.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Japanese cohort; A total of 12 Japanese healthy subjects will be allocated to receive 3 ascending single doses (100 mg, 300 mg and 750 mg) of PF-04991532 or placebo through 3 dosing periods in a randomization ratio of 3:1.	Drug: PF-04991532; Single dose administration of PF-04991532 (100 mg, 300 mg and 750 mg) in tablet formulation under fasted condition.; Drug: Placebo; Single dose administration of matching placebo in tablet formulation at the fasted state; Drug: PF-04991532; Single dose administration of PF-04991532 (300 mg and 750 mg) in tablet formulation under fasted condition.
EXPERIMENTAL: Weterner Cohort; 9 western healthy subjects will be enrolled to receive 2 single ascending doses (300 mg and 750 mg) of PF-04991532 through 2 dosing periods.	Drug: PF-04991532; Single dose administration of PF-04991532 (100 mg, 300 mg and 750 mg) in tablet formulation under fasted condition.; Drug: PF-04991532; Single dose administration of PF-04991532 (300 mg and 750 mg) in tablet formulation under fasted condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours post dose
Time for Cmax (Tmax)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours
Area under the plasma concentration-time profile from time zero to 24 hours (AUC0-24)	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12 and 16, 24, 36 and 48 hours
Total amount of unchanged drug excreted in the urine over 24 hours, expressed as percent of dose (Ae24%)	Urine collection from 0 to 24 hours post dose
Renal clearance (CLr)	Urine collection from 0 to 24 hours post dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 7, 2011
• First Posted (ESTIMATE): June 8, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 22, 2011
• Last Update Submitted That Met QC Criteria: September 20, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: PK; Japanese and Western population; safety and tolerability; PF-04991532
• Additional Relevant MeSH Terms: Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Micronutrients; Vitamins; Vitamin B Complex; Nicotinic Acids; 6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid
• Other Study ID Numbers: B2611013