Multiple Dose Study of PF-04991532 in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT01129258
First received: May 21, 2010
Last updated: March 8, 2011
Last verified: March 2011
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Phase 1 Placebo-Controlled Trial to Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses of PF-04991532 in Adult Patients With Type 2 Diabetes Mellitus (T2DM)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Single-Dose PK Endpoints for PF-04991352: Cmax, Tmax, and AUC(0-tau). [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin and C-peptide (changes from Day -1 baseline) during an MMTT on Days 1 and 14. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Mean daily glucose (change from Day -1 baseline) on Days 1 and 14. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Fasting plasma glucose (change from Day -1 baseline) on Days 1, 3, 6, 10, and 14. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Lactate (change from Day -1 baseline), at times specified in the SOA. [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]

Enrollment: 110
Study Start Date: June 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-04991532 Drug: PF-04991532
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 Comparator: Placebo Drug: 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.

Detailed Description:

Safety/Tolerability, PK, and PD

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with type 2 diabetes mellitus who are taking metformin only. Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in combination with metformin may be eligible if washed off the SU or DPP-4i to metformin only for a minimum of 4 weeks before dosing. Subjects being switched over from an SU and metformin or a DPP-4i and metformin to metformin only will still need to meet the fasting glucose requirements on Day -2 as defined in the protocol.
  • Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
  • Fasting C-peptide >0.8 ng/mL.
  • HbA1c >/=7% and >/=10%. If the patient requires to be washed off an SU or DPP-4i, the HbA1c limits will be >/=6.5% and </=9%.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. Subjects who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well.
  • Evidence or history of diabetic complications with significant end-organ damage.
  • Any condition possibly affecting drug absorption (eg, gastrectomy).
  • History of stroke, transient ischemic attack, or myocardial infarction within the past 6 months.
  • History of coronary artery bypass graft or stent implantation.
  • Clinically significant peripheral vascular disease.
  • Any history or clinical evidence of congestive heart failure, NYHA Classes II-IV.
  • Current history of angina/unstable angina.
  • ECG findings suggestive of asymptomatic myocardial ischemia or QTc >470 msec at screening.
  • One or more self-reported episodes of hypoglycemia within the last 3 months, or two or more self-reported episodes of hypoglycemia within the last 6 months.
  • Screening or Day -2 fasting (>/=8 hours) glucose, </=90 or >/=270 mg/dL, confirmed by a single repeat if deemed necessary.
  • A positive urine drug screen.
  • Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day.
  • 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.
  • Certain concomitant medications are excluded, as defined in the protocol.
  • Screening supine blood pressure >/=160 mm Hg (systolic) or >/=100 mm Hg (diastolic).
  • Certain laboratory values (for example, triglyceride and liver function test results).
  • Pregnant or nursing females; females of childbearing potential.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01129258

Locations
United States, California
Pfizer Investigational Site
Chula Vista, California, United States, 91911
Pfizer Investigational Site
Fountain Valley, California, United States, 92708
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT01129258     History of Changes
Other Study ID Numbers: B2611004
Study First Received: May 21, 2010
Last Updated: March 8, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
phase 1
safety and tolerability
pharmacokinetics
PK
pharmacodynamics
PD
type 2 diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 15, 2014