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

• ClinicalTrials.gov Identifier: NCT01933672
• Recruitment Status: Completed
• First Posted: September 2, 2013
• Results First Posted: September 27, 2016
• Last Update Posted: September 27, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

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

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: PF-04937319 once-daily; Drug: PF-04937319 split-dose; Drug: Sitagliptin once-daily	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• 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 Start Date: October 2013
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: PF-04937319 once-daily	Drug: PF-04937319 once-daily; Tablets, 300 mg once-daily with breakfast, 14-days
Experimental: PF-04937319 split-dose	Drug: PF-04937319 split-dose; tablets, 150 mg with breakfast plus 100 mg with lunch, 14-days
Active Comparator: Sitagliptin once-daily	Drug: Sitagliptin once-daily; tablets, 100 mg once-daily with breakfast, 14-days

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Weighted Mean Daily Glucose (WMDG) at Day 14 [ 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 ]
   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 :

1. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 [ Time Frame: 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.
2. Change From Baseline in Pre-meal C-Peptide on Day 14 [ Time Frame: 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.
3. Change From Baseline in Pre-meal Insulin on Day 14 [ Time Frame: 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.
4. Incidence of All Causality Treatment-Emergent Adverse Event by Preferred Term (Frequency Rate >5%) [ Time Frame: Day 1 up to Day 14 ]
5. Frequency of Laboratory Test Abnormalities Reported in Any Treatment Group [ Time Frame: Day 1 up to Day 14 ]
   The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed.
6. Change From Baseline in Body Weight (kg) [ Time Frame: Day 1 up to Day 14 ]
7. Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern [ Time Frame: Day 1 up to Day 14 ]
   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).
8. Number of Participants With Post-baseline Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern [ Time Frame: Day 1 up to Day 14 ]
   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.
9. Plasma PF-04937319 Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC24) of PF-04937319 at Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
   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.
10. Plasma PF-04937319 Apparent Clearance (CL/F) on Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
    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.
11. Plasma PF-04937319 Average Concentration Over the 24-hour Period (Cav) on Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
    Cav was average concentration over the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
12. Plasma PF-04937319 Highest Observed Concentration (Cmax) on Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
    Cmax was highest observed concentration. The PK parameters were summarized descriptively by treatment as appropriate.
13. Plasma PF-04937319 Lowest Observed Concentration During the 24-hour Period (Cmin) on Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
    Cmin lowest observed concentration during the 24-hour period. The PK parameters were summarized descriptively by treatment as appropriate.
14. Plasma PF-04937319 Time for Cmax (Tmax) on Day 14 [ Time Frame: Predose, 1.5, 3, 5, 6.5, 8, 11, 12.5, and 14 hours on Days 0 and 14; and predose on Days 7 and 15. ]
    Tmax was time of maximum concentration. The PK parameters were summarized descriptively by treatment as appropriate.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Florida

Avail Clinical Research, LLC

DeLand, Florida, United States, 32720

Miami Research Associates, Inc.

South Miami, Florida, United States, 33143

MRA Clinical Research, LLC

South Miami, Florida, United States, 33143

United States, North Carolina

High Point Clinical Trials Center, LLC

High Point, North Carolina, United States, 27265

United States, Ohio

Community Research

Cincinnati, Ohio, United States, 45255

United States, Texas

Clinical Trials of Texas, Inc

San Antonio, Texas, United States, 78229

Diabetes and Glandular Disease Clinic

San Antonio, Texas, United States, 78229

United States, Wisconsin

Spaulding Clinical Research, LLC

West Bend, Wisconsin, United States, 53095

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01933672
• Other Study ID Numbers: B1621019
• First Posted: September 2, 2013
• Results First Posted: September 27, 2016
• Last Update Posted: September 27, 2016
• Last Verified: August 2016

Keywords provided by Pfizer:

Phase 1b; type 2 diabetes; metformin background; PF-04937319

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action