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.

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: PF-04937319 IR MST
* Drug: PF-04937319 MR 1
* Drug: PF-04937319 MR 2
* Drug: PF-04937319 MR 3


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, PF-04937319, bioavailability, type 2 diabetes mellitus