Study To Compare Single Dose Of Three Modified Release Formulations Of PF-04937319 With Immediate Release Material-Sparing-Tablet (IR MST) Formulation Previously Studied In Adults With Type 2 Diabetes Mellitus.

A Phase 1, Randomized, Open-label, Cross-over, Single-day Study Of Pf-04937319 To Characterize Relative Bioavailability, Tolerability, And Pharmacodynamics Of Four Oral Formulations In Adults With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin

Study B1621015 will characterize bioavailability, tolerability and pharmacodynamics of three modified release formulations of PF-04937319 compared with the immediate release material-sparing-tablet (IR MST) formulation in adults with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: PF-04937319 IR MST; Drug: PF-04937319 MR 1; Drug: PF-04937319 MR 2; Drug: PF-04937319 MR 3

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults with type 2 diabetes, on stable background metformin therapy either alone or in combination with another oral anti-diabetic agent (OAD) excluding thiazolidinediones (TZDs)

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-04937319 IR MST; Reference formulation	Drug: PF-04937319 IR MST; Immediate release material sparing tablet (IR MST) administered as 150 mg with morning meal and 100 mg with lunch
Experimental: PF-04937319 MR 1; Test MR #1	Drug: PF-04937319 MR 1; Modified release formulation #1 administered with the morning meal at a dose predicted to yield exposure (AUC24) equivalent to 300 mg IR MST
Experimental: PF-04937319 MR 2; Test MR #2	Drug: PF-04937319 MR 2; Modified release formulation #2 administered with the morning meal at a dose predicted to yield exposure (AUC24) equivalent to 300 mg IR MST
Experimental: PF-04937319 MR 3; Test MR #3	Drug: PF-04937319 MR 3; Modified release formulation #3 administered with the morning meal at a dose predicted to yield exposure (AUC24) equivalent to 300 mg IR MST

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf]	AUCinf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.	0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
Change From Reference in Weighted-Mean-Daily-Glucose (WMDG) on Day 1	MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed.	0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, and 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed PF-04937319 Plasma Concentration (Cmax)		0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
PF-04937319 Plasma Concentration at 5 Hours After Morning Dose (C5)		0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
PF-04937319 Plasma Concentration at 16 Hours After Morning Dose (C16)		0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
PF-04937319 Plasma Concentration at 24 Hours After Morning Dose (C24)		0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
Ratio of Maximum to Approximate Trough PF-04937319 Concentration (Cmax/C24)	Cmax/C24 is the ratio of maximum to approximate trough concentration, where Cmax is the overall maximum observed plasma concentration and C24 is the plasma concentration at 24 hours after the morning dose.	0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
Time to Reach Maximum Observed PF-04937319 Plasma Concentration (Tmax)		0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable PF-04937319 Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
Terminal Elimination Half-Life (t1/2)	t1/2 is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 11, 12.5, 14, 16, 20, 24, 36, 48, and 72 hours post-dose
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 drug. 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 drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.	Baseline up to 28 days after last study drug administration in Period 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Estimate): March 4, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Phase 1; type 2 diabetes mellitus; bioavailability; PF-04937319
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: B1621015