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

NCT01044537 | Completed Phase 1 Results

• 1 other identifier: B1621001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Type 2 Diabetes Mellitus

Keywords

phase 1; safety and tolerability; PK; PD; type 2 diabetes mellitus; T2DM

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 10 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  Day 1 up to 10 days after last dose of study medication (up to 11 days)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

  Area under the plasma concentration-time curve from zero to the last measured concentration (AUClast).

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Maximum Observed Plasma Concentration (Cmax)

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Apparent Oral Clearance (CL/F)

  Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Apparent Volume of Distribution (Vz/F)

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Plasma Decay Half-Life (t1/2)

  Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half.

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)

  AUCinf is the area under the plasma concentration versus time curve from time zero to extrapolated infinite time.

  0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose

Secondary Outcomes (7)

• Change From Baseline in Ratio of C-peptide Area Under Curve (C-peptide AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1

  -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hours pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hours post-dose on Day 1

• Percent Change From Baseline in Post-Prandial Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1

  -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

• Percent Change From Baseline in Post-Prandial Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1

  -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

• Percent Change From Baseline in Post-Prandial C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1

  -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1

• Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1

  -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1

Study Arms (2)

Placebo

PLACEBO COMPARATOR

In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo.

Drug: Placebo

PF-04937319

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo to match PF-04937319 will be provided.

Placebo

PF-04937319 DRUG

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.

PF-04937319

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Dedicated Phase 1

Phoenix, Arizona, 85013, United States

Location

West Coast Clinical Trials, LLC

Cypress, California, 90630, United States

Location

Elite Research Institute

Miami, Florida, 33169, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2010
• First Posted: January 8, 2010
• Study Start: February 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 10, 2017
• Results First Posted: March 10, 2017

Record last verified: 2017-01

Locations

US (3)