A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT01044537
First received: January 7, 2010
Last updated: June 7, 2010
Last verified: June 2010
  Purpose

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-04937319 following single escalating oral doses in adult subjects with Type 2 Diabetes Mellitus (T2DM).


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: A Phase 1 Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Escalating Oral Doses Of PF-04937319 In Adult Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Safety and tolerability of PF-04937319 will be assessed by physical examinations, adverse event monitoring, 12 lead ECGs, continuous cardiac monitoring, vital sign, and safety laboratory measurements. [ Time Frame: ~4 months ] [ Designated as safety issue: Yes ]
  • The single dose pharmacokinetics (PK) of PF-04937319 will be described by estimating parameters of AUCinf, AUClast, AUC24, Cmax, Tmax, CL/F, Vz/F and half life (t1/2), as the data permit. [ Time Frame: ~4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary pharmacodynamic (PD) endpoints will include glucose, insulin, and C-peptide in response to a mixed meal tolerance test (MMTT). [ Time Frame: ~4 months ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: February 2010
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo.
Drug: Placebo
Placebo to match PF-04937319 will be provided.
Other Name: Placebo
Experimental: PF-04937319
In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo. There will be approximately 6 dosing levels of PF-04937319
Drug: PF-04937319
The initial planned dosing schedule is: 10, 30, 100, 200, and 400 mg, with one cohort to be determined. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as a single oral dose as a powder-in-capsule (PIC) formulation. PF-04937319 will be supplied as 10 mg and 80 mg (and potentially 1 mg) PIC.
Other Name: PF-04937319

Detailed Description:

The purpose of this phase 1 study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF04937319 following single escalating oral doses in adult subjects with T2DM.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with type 2 diabetes mellitus who are taking stable doses of metformin only. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-IV inhibitor (DPP-IVi) in combination with metformin may be eligible if washed off the SU or DPP-IVi to metformin only for a minimum of 4 weeks before dosing.
  • Male and/or female subjects (females will be women of non childbearing potential) between the ages of 18 and 65 years, inclusive, with a body mass index (BMI) of 18.5 to 45.0 kg/m2 and C-peptide >0.8 ng/mL.
  • Screening and Day -2 troponin I concentration </=0.05 ng/mL as measured by the Bayer Centaur Ultra assay.
  • HbA1c >/=7% and </=11%. If the patient requires to be washed off an SU or DPP-IVi, the HbA1c limits will be >/=7% and </=9.5%.

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).
  • Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance </=60 mL/min based on the Cockcroft-Gault equation, diabetic neuropathy complicated by neuropathic ulcers.
  • History of stroke, transient ischemic attack, or myocardial infarction within the past 6 months. Additionally, history of coronary artery bypass graft or stent implantation, clinically significant peripheral vascular disease, or congestive heart failure (NYHA Classes II-IV). Furthermore, a current history of angina/unstable angina. Also, 12 lead electrocardiogram (ECG) demonstrating QTc >450 msec at screening, ECG findings suggestive of asymptomatic myocardial ischemia, or supine blood pressure >/=160 mm Hg (systolic) or </=100 mm Hg (diastolic).
  • 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) blood glucose, </=70 or >/=270 mg/dL, confirmed by a single repeat if deemed necessary.
  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: NCT01044537

Locations
United States, Arizona
Pfizer Investigational Site
Phoenix, Arizona, United States, 85013
United States, California
Pfizer Investigational Site
Cypress, California, United States, 90630
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
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: NCT01044537     History of Changes
Other Study ID Numbers: B1621001
Study First Received: January 7, 2010
Last Updated: June 7, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
phase 1
safety and tolerability
PK
PD
type 2 diabetes mellitus
T2DM

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

ClinicalTrials.gov processed this record on October 19, 2014