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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Placebo

PF-04937319

About this trial

This is an interventional other trial for Type 2 Diabetes Mellitus focused on measuring phase 1, safety and tolerability, PK, PD, type 2 diabetes mellitus, T2DM

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Dedicated Phase 1
West Coast Clinical Trials, LLC
Elite Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

PF-04937319

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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).

Maximum Observed Plasma Concentration (Cmax)

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Apparent Oral Clearance (CL/F)

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

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.

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.

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.

Secondary Outcome Measures

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

Ratio of area under the plasma C-peptide concentration-time curve from time 2 to 6 hrs (in terms of nanogram*deciliter*hour [ng*dL*hour]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram*milliliter*hour [mg*mL*hour]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at 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

Percent change from baseline in post-prandial area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated 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

Percent change from baseline in post-prandial area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated 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

Percent change from baseline in post-prandial area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated 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

Ratio of insulin delta C30 (in terms of milliunits*deciliter [mU*dL]) to glucose delta C30 (in terms of milligram*liter [mg*liter]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.

Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT)

Ratio of C-peptide Delta C30 (in terms of nanogram*deciliter [ng*dL]) to glucose delta C30 (in terms of milligram*milliliter [mg*mL]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.

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

Ratio of area under the plasma insulin concentration-time curve from time 2 to 6 hrs (in terms of milliunit*deciliter*hour [mU*dL*hour]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram*liter*hour [mg*liter*hour]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at Day 1.

Full Information

NCT ID

NCT01044537

First Posted

January 7, 2010

Last Updated

January 20, 2017

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01044537

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

May 2010 (Actual)

Study Completion Date

May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

PF-04937319

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo to match PF-04937319 will be provided.

Intervention Type

Drug

Intervention Name(s)

PF-04937319

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

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

Time Frame