Study Of Two Dosing Regimens Of PF-04937319 Compared To An Approved Agent (Sitagliptin) In Patients With Type 2 Diabetes

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

PF-04937319 once-daily

PF-04937319 split-dose

Sitagliptin once-daily

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Phase 1b, type 2 diabetes, metformin background, PF-04937319

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with type 2 diabetes, on background metformin therapy either alone or with 1 other oral anti-diabetic agent (excluding Actos)

Exclusion Criteria:

Patients with cardiovascular event within 6-months of screening
Patients with diabetic complications
Female subjects who are pregnant or planning to become pregnant
Subjects with unstable medical conditions (eg, hypertension)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

PF-04937319 once-daily

PF-04937319 split-dose

Sitagliptin once-daily

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14

Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours.

Secondary Outcome Measures

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14

Blood samples for measurement of glucose to permit derivation of pre-meal collections at the pre-specified nominal timepoints of each period: predose (ie, time "0"), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours on Day 0 (baseline) and Day 14; and predose on Days 1 and 15.

Change From Baseline in Pre-meal C-Peptide on Day 14

Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for C-peptide at the pre-specified nominal timepoints at predose, 5 and 11 hours on Day 0 (baseline) and Day 14.

Change From Baseline in Pre-meal Insulin on Day 14

Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for insulin at 0, 5 and 11 hours on Day 0 (baseline) and Day 14.

Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)

Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group

The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed.

Change From Baseline in Body Weight (kg)

Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern

Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: sitting systolic BP (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, sitting SBP =<20 mmHg change from baseline, supine/sitting/standing SBP less than (<) 90 mm Hg; sitting diastolic BP (DBP) >=20 mm Hg change from baseline, sitting SBP =<20 mmHg change from baseline, supine/sitting/standing DBP <50 mm Hg; 2), pulse rate (supine): <40 or greater than (>) 120 beats per minute (bpm).

Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern

ECG criteria of potential clinical concern were 1), PR interval: >=300 milliseconds (msec); >=25% increase when baseline >200 msec; or increase >=50% when baseline <=200 msec; 2), QRS interval: >=140 msec; >=50% increase from baseline; 3), QTc interval using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; absolute change 30 - <60, >=60 msec.

Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14

The PK parameters were summarized descriptively by treatment as appropriate. Two (2) PK parameters specified in the protocol and SAP were not reported: AUClast was not reported since it was the same as AUC24 in this study, and apparent volume of distribution (Vz/F) was not reported since the log-linear terminal phase of the concentration-time profiles was not consistently well characterized in the 24-hour sampling period.

Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14

The PK parameters were summarized descriptively by treatment as appropriate. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14

Cav was average concentration over the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.

Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14

Cmax was highest observed concentration. The PK parameters were summarized descriptively by treatment as appropriate.

Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14

Cmin lowest observed concentration during the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.

Plasma PF-04937319 Time for Cmax (Tmax) on Day 14

Tmax was time of maximum concentration. The PK parameters were summarized descriptively by treatment as appropriate.

Full Information

NCT ID

NCT01933672

First Posted

August 28, 2013

Last Updated

August 3, 2016

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01933672

Brief Title

Study Of Two Dosing Regimens Of PF-04937319 Compared To An Approved Agent (Sitagliptin) In Patients With Type 2 Diabetes

Official Title

A Phase 1b, Randomized, Double-blind, Active Comparator Controlled, 3-period, Cross-over Study To Characterize The Pharmacodynamics And Tolerability Of Two Dosing Regimens Of Pf-04937319 In Adults With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

October 2013 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

Study B1621019 will assess efficacy and safety of two different dosing regimens of an investigational agent (PF-04937319) compared to an approved drug (sitagliptin) in patients with type 2 diabetes

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 1b, type 2 diabetes, metformin background, PF-04937319

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PF-04937319 once-daily

Arm Type

Experimental

Arm Title

PF-04937319 split-dose

Arm Type

Experimental

Arm Title

Sitagliptin once-daily

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

PF-04937319 once-daily

Intervention Description

Tablets, 300 mg once-daily with breakfast, 14-days

Intervention Type

Drug

Intervention Name(s)

PF-04937319 split-dose

Intervention Description

tablets, 150 mg with breakfast plus 100 mg with lunch, 14-days

Intervention Type

Drug

Intervention Name(s)

Sitagliptin once-daily

Intervention Description

tablets, 100 mg once-daily with breakfast, 14-days

Primary Outcome Measure Information:

Title

Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14

Description

Plasma glucose concentration was determined predose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours postdose on Days 0 (baseline) and 14. WMDG was calculated as the area under the curve (AUC) of the 12-point plasma glucose concentration-time profile divided by 24 hours.

Time Frame

Prior to morning dose (Hour 0) and at 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16, 20, and 24 hours post morning dose on Days 0 (baseline) and Day 14

Secondary Outcome Measure Information:

Title

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14

Description

Blood samples for measurement of glucose to permit derivation of pre-meal collections at the pre-specified nominal timepoints of each period: predose (ie, time "0"), 1.5, 3, 5, 6.5, 8, 11, 12.5, 14, 16 and 20 hours on Day 0 (baseline) and Day 14; and predose on Days 1 and 15.

Time Frame

Day 14

Title

Change From Baseline in Pre-meal C-Peptide on Day 14

Description

Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for C-peptide at the pre-specified nominal timepoints at predose, 5 and 11 hours on Day 0 (baseline) and Day 14.

Time Frame

Day 14

Title

Change From Baseline in Pre-meal Insulin on Day 14

Description

Blood samples for measurement of glucose to permit derivation of pre-meal collections of blood samples for insulin at 0, 5 and 11 hours on Day 0 (baseline) and Day 14.

Time Frame

Day 14

Title

Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%)

Time Frame

Day 1 up to Day 14

Title

Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group

Description

The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed.

Time Frame

Day 1 up to Day 14

Title

Change From Baseline in Body Weight (kg)

Time Frame

Day 1 up to Day 14

Title

Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern

Description

Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: sitting systolic BP (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, sitting SBP =<20 mmHg change from baseline, supine/sitting/standing SBP less than (<) 90 mm Hg; sitting diastolic BP (DBP) >=20 mm Hg change from baseline, sitting SBP =<20 mmHg change from baseline, supine/sitting/standing DBP <50 mm Hg; 2), pulse rate (supine): <40 or greater than (>) 120 beats per minute (bpm).

Time Frame

Day 1 up to Day 14

Title

Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern

Description

ECG criteria of potential clinical concern were 1), PR interval: >=300 milliseconds (msec); >=25% increase when baseline >200 msec; or increase >=50% when baseline <=200 msec; 2), QRS interval: >=140 msec; >=50% increase from baseline; 3), QTc interval using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; absolute change 30 - <60, >=60 msec.

Time Frame

Day 1 up to Day 14

Title

Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14

Description

The PK parameters were summarized descriptively by treatment as appropriate. Two (2) PK parameters specified in the protocol and SAP were not reported: AUClast was not reported since it was the same as AUC24 in this study, and apparent volume of distribution (Vz/F) was not reported since the log-linear terminal phase of the concentration-time profiles was not consistently well characterized in the 24-hour sampling period.

Time Frame