Single Dose Study of PF-04991532 in Healthy Subjects

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01102673

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders	Drug: PF-04991532 Drug: Placebo	Phase 1

Detailed Description

Safety/Tolerability and PK

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Official Title:

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

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

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

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

Drug: Placebo

Placebo to match PF-04991532 will be provided

Outcome Measures

Primary Outcome Measures

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

none-see my comment []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.