Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01272804
First received: January 6, 2011
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04937319 following multiple (14 days) escalating oral doses in patients with type 2 diabetes.


Condition Intervention Phase
Diabetes Mellitus, Type 2
NIDDM
Drug: PF-04937319
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1 Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses Of PF-04937319 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 04937319 will be assessed by physical examinations, adverse event and hypoglycemia monitoring, 12 lead ECGs, vital sign, and clinical safety laboratory measurements. [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
  • Single Dose PK endpoints: Cmax, Tmax, and AUC(0-Tau) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Day 6 PK Endpoints: Cmax, Tmax, and AUC(0-8) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Multiple Dose PK Endpoints: Cmax(ss), Tmax(ss), AUC(0-Tau,ss), AUC(0-8), AUC(0-last), half life, Cmin(ss), Cav(ss), Ae%, CL/F, Vz/F; 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 ]
  • Average daily glucose (change from Day -1 baseline) on Days 1, 6, and 14. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Fasting plasma glucose (change from Day 1 pre dose baseline) on Days 1 through 15. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Lipids (change from baseline), including: TG, TC, HDL cholesterol, and LDL cholesterol, at times specified in the SOA. [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
  • Lactate (change from baseline), at times specified in the SOA. [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]

Enrollment: 61
Study Start Date: February 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-04937319 Drug: PF-04937319
Subjects will be dosed with PF-04937319 for 14 days. The doses planned are 10, 30, 100 and 300 mg QD. All doses will be administered as tablets (10 and 100 mg strengths). In each Cohort, 9 patients will receive PF 04937319 and 3 will receive placebo. An additional cohort of 12 patients (9 active, 3 placebo) may be performed to explore a QD or BID dose. The dose for this additional cohort could be a dose already studied or a new dose that is within the exposure stopping criteria.
Placebo Comparator: Placebo Drug: Placebo
Placebo to match PF-04937319 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04937319 and 3 will receive placebo.

  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. Regimens may include once daily and twice daily dosing only.
  • Male and/or female patients (females will be women of non childbearing potential)
  • Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
  • HbA1c between 7.0% and 10.0%.

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). Patients 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 (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).
  • Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance less than 60 mL/min
  • Any condition possibly affecting drug absorption (eg, gastrectomy)
  • History of stroke or 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 (eg, manifested by claudication).
  • Any history or clinical evidence of congestive heart failure, NYHA Classes II to IV.
  • One or more self reported significant/severe/requiring treatment episodes of hypoglycemia within the last 3 months, or two or more self reported significant/severe/requiring treatment episodes of hypoglycaemia within the last 6 months.
  • Current history of angina/unstable angina.
  • Milk or soy allergy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01272804

Locations
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
Pfizer Investigational Site
South Miami, Florida, United States, 33143
United States, Ohio
Pfizer Investigational Site
Cincinnati, Ohio, United States, 45212
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01272804     History of Changes
Other Study ID Numbers: B1621003
Study First Received: January 6, 2011
Last Updated: January 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Pharmacokinetics PK Pharmacodynamics PD T2DM Phase 1 Type 2 diabetes mellitus safety and tolerability

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

ClinicalTrials.gov processed this record on July 24, 2014