The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04991532 following multiple (14 days) escalating oral doses in patient wtih type 2 diabetes.
Safety/Tolerability, PK, and PD
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
DOUBLE
Enrollment
110
Subjects will be dosed wtih PF-04991532 for 14 days. The tentative dosing schedule is 30, 100, 300, 1000, and 1500 mg QD, and 150 and 500 mg BID). Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as tablets (10, 50, and 150 mg strengths). In each cohort 9 subjects will receive PF-04991532 and 3 will receive placebo.
Placebo to match PF-04991532 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04991532 and 3 will receive placebo.
Pfizer Investigational Site
Chula Vista, California, United States
Pfizer Investigational Site
Fountain Valley, California, United States
Pfizer Investigational Site
Miami, Florida, United States
Pfizer Investigational Site
San Antonio, Texas, United States
Safety Endpoints: Safety and tolerability of PF-04991532 will be assessed by physical examinations, adverse event monitoring, 12-lead ECGs, vital sign, and clinical safety laboratory measurements.
Time frame: 5 months
Single-Dose PK Endpoints for PF-04991352: Cmax, Tmax, and AUC(0-tau).
Time frame: 5 months
Multiple-Dose PK Endpoints for PF-04991532: Cmax(ss), Tmax(ss), AUC(0-tau,ss), AUC(0-last), half-life, Cmin(ss), Cav(ss), Ae%, CL/F, Vz/F, CLrenal; accumulation ratios AUC(0-tau,ss)/AUC(0-tau,sd) and Cmax(ss)/Cmax(sd), as the data permit.
Time frame: 5 months
PD Endpoint: glucose excursion (change from Day -1 baseline) in response to a liquid meal test (MMTT) on Days 1 and 14.
Time frame: 5 months
Insulin and C-peptide (changes from Day -1 baseline) during an MMTT on Days 1 and 14.
Time frame: 5 months
Mean daily glucose (change from Day -1 baseline) on Days 1 and 14.
Time frame: 5 months
Fasting plasma glucose (change from Day -1 baseline) on Days 1, 3, 6, 10, and 14.
Time frame: 5 months
Lipids (change from Day -1 baseline), including: TG, TC, HDL-cholesterol, LDL-cholesterol, FFA, beta-OHB, and ACAC, at times specified in the SOA.
Time frame: 5 months
Lactate (change from Day -1 baseline), at times specified in the SOA.
Time frame: 5 months
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