A Multiple Dose Study Of PF-04620110 In Type 2 Diabetes Patients

Study Overview
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Brief Summary
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PF-04620110 is a novel compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this trial is to evaluate the safety and tolerability, and pharmacodynamics, of multiple oral doses of PF-04620110 in T2DM patients.

Official Title
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A Phase 1B, Randomized, Double-Blind, Placebo-Controlled Trial To Assess The Efficacy And Safety Of 4-Week Administration Of Multiple Oral Doses Of PF-04620110 In Type 2 Diabetes Mellitus Subjects With Insufficient Glycemic Control On Metformin

Conditions
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Type 2 Diabetes Patients

Intervention / Treatment
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* Drug: PF-04620110
* Drug: PF-04620110
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female subjects between the ages of 18 and 60 years; Body Mass Index (BMI) of >25.0 kg/m2 and <40 kg/m2; Subjects must have a historical diagnosis of T2DM in accordance with the ADA guidelines; Subjects who have been on well-tolerated and stable doses of metformin Exclusion Criteria: Recent evidence (6 months prior to screening) or history of unstable major organ disease; Diagnosis of Type 1 diabetes mellitus; Current medical history of myocardial infarction, unstable angina, or history of stroke (including TIA) within 6 months prior to Screening; Treatment with thiazolidinediones (TZDs), or subcutaneously administered antidiabetic agents;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04620110<br> | Drug: PF-04620110<br>* 5 mg of PF-04620110 given once daily<br>Drug: PF-04620110<br>* 2.5 mg of PF-04620110 given twice daily<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Matching placebo giving for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Post-Prandial Glucose Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 | 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 (Day -1); 2 to 6 hours post-dose on Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-Hour Average Plasma Glucose (APG) Post-Dose at Day 28 | APG= AUC (0-24)/24. AUC (0-24) was computed using Linear trapezoidal method. | Baseline (Day -1); 24 hours post-dose on Day 28 | 
| Change From Baseline in Post-Prandial Insulin Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 | Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. | Baseline (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Post-Prandial C-Peptide Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 | 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 (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Post-Prandial Net Triglyceride Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) After a Mixed Meal Tolerance Test (MMTT) at Day 28 | Change from baseline in post-prandial area under the plasma net triglyceride concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. | Baseline (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Total Amide Glucagon Like Peptide-1 (GLP-1) and Active Glucagon Like Peptide-1 (GLP-1) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 | Change from baseline in total amide GLP-1 and active GLP-1 area under the plasma concentration time curve was computed by Linear trapezoidal method. | Baseline (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Gastric Inhibitory Peptide (GIP) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 | Change from baseline in GIP area under the plasma concentration time curve was computed by Linear trapezoidal method. | Baseline (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Peptide YY (PYY) Area Under the Concentration-Time Curve From Time 2 to 6 Hours (AUC 2-6) at Day 28 | Change from baseline in PYY area under the plasma concentration time curve was computed by Linear trapezoidal method. | Baseline (Day -1); 2 to 6 hours post-dose on Day 28 | 
| Change From Baseline in Fasting Glucose at Day 28 |  | 0 hour (pre-dose) on Day -1, Day 28 | 
| Change From Baseline in Fasting Insulin at Day 28 |  | 0 hour (pre-dose) on Day -1, Day 28 | 
| Change From Baseline in Fasting Net Triglycerides at Day 28 |  | 0 hour (pre-dose) on Day -1, Day 28 | 
| Change From Baseline in Post-Lunch Glucose Excursions Area Under the Concentration-Time Curve From Time 6 to 10 Hours (AUC 6-10) Post-dose at Day 28 | Change from baseline in post-lunch glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method. | Baseline (Day -1); 6 to 10 hours post-dose on Day 28 | 
| Change From Baseline in Post-Dinner Glucose Excursions Area Under the Concentration-Time Curve From Time 12 to 16 Hours (AUC 12-16) Post-dose at Day 28 | Change from baseline in post-dinner glucose excursion under the plasma concentration time curve was computed by Linear trapezoidal method. | Baseline (Day -1); 12 to 16 hours post-dose on Day 28 | 
| Maximum Observed Plasma Concentration (Cmax) of PF-04620110 |  | 24 hours post-morning dose on Day 28 | 
| Minimum Observed Plasma Trough Concentration (Cmin) of PF-04620110 |  | 24 hours post-morning dose on Day 28 | 
| Time to Cmax (Tmax) of PF-04620110 |  | 24 hours post-morning dose on Day 28 | 
| Area Under the Concentration-Time Curve AUC (0-24) of PF-04620110 | Area under the plasma concentration-time curve from time 0 (pre-dose) to 24 hours. AUC (0-24) was computed using the linear trapezoidal method. | 24 hours post-morning dose on Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple dose study in type 2 diabetes patients