Single Dose Study of PF-04991532 in Healthy Subjects

A Phase 1 Placebo-Controlled Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Food Effect of Single Escalating Oral Doses of PF-04991532 in Healthy Adult Subjects

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK) and preliminary food effect of PF-04991532 following single escalating oral doses in healthy adult subjects.

Study Overview

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

Detailed Description

Safety/Tolerability and PK

• Study Type: Interventional
• Enrollment (Anticipated): 18
• 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 (non child-bearing potential) 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 17.5 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 (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.
• Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.
• Self-reported history of hypoglycemia, or fasting laboratory glucose value </=80 mg/dL at screening or Day 0 of Period 1, confirmed by a single repeat if deemed necessary.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-04991532; This will be a crossover study with 2 cohorts and an interleaving design with placebo substitution. The study will be conducted over 4 treatment periods in Cohort 1 (n=9) and over 3 treatment periods in Cohort 2 (n=9). Six subjects will be allocated to receive PF-04991532 and three subjects will be allocated to receive placebo treatment during each dosing period, except for the 4th period of Cohort 1. The 4th period of Cohort 1 will be dedicated to assess the effect of food on PF-04991532 PK parameters at one of the doses previously tested in Cohort 1; hence all 9 subjects will be dosed with PF-04991532 in an open-label fashion. A washout period of at least 7 days will occur between each dose.	Drug: PF-04991532; The tentative dosing schedule is 30, 100, 300, 600, 1200, and 2000 mg. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as extemporaneously-prepared powder in capsule (PIC) formulation.
Placebo Comparator: Placebo; This will be a crossover study with 2 cohorts and an interleaving design with placebo substitution. The study will be conducted over 4 treatment periods in Cohort 1 (n=9) and over 3 treatment periods in Cohort 2 (n=9). Six subjects will be allocated to receive PF-04991532 and three subjects will be allocated to receive placebo treatment during each dosing period, except for the 4th period of Cohort 1. The 4th period of Cohort 1 will be dedicated to assess the effect of food on PF-04991532 PK parameters at one of the doses previously tested in Cohort 1; hence all 9 subjects will be dosed with PF-04991532 in an open-label fashion. A washout period of at least 7 days will occur between each dose.	Drug: Placebo; Placebo to match PF-04991532 will be provided

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability Endpoints: physical exams, AE monitoring, 12-lead ECGs, continuous cardiac monitoring, vital sign and clinical safety laboratory (including frequent glucose assessments via glucometer) measurements.	1 month
PK Endpoints: AUC(0-inf), AUC(0-last), AUC(0-24), Cmax, Tmax, CL/F, Vz/F and half-life (t1/2), as the data permit.	1 month

Secondary Outcome Measures

Outcome Measure
none-see my comment

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: April 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: April 12, 2010
• First Submitted That Met QC Criteria: April 12, 2010
• First Posted (Estimate): April 13, 2010

Study Record Updates

• Last Update Posted (Estimate): August 5, 2010
• Last Update Submitted That Met QC Criteria: August 3, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: PK; phase 1; type 2 diabetes mellitus; T2DM; safety and tolerability
• Additional Relevant MeSH Terms: Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; 6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid
• Other Study ID Numbers: B2611001