Phase 2 Study To Evaluate Safety And Efficacy Of Investigational Drug - PF04937319 In Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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B1621007 is designed to study the safety and efficacy of PF-04937319 in patients with type 2 diabetes

Official Title
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A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-ranging, Parallel Group Study To Evaluate Safety And Efficacy Of Pf-04937319 And Sitagliptin On Glycemic Control In Adult Patients 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: Placebo
* Drug: PF-04937319 - 3mg
* Drug: PF-04937319 - 20mg
* Drug: PF-04937319 - 50mg
* Drug: PF-04937319 - 100mg
* Drug: Sitagliptin - 100mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with type 2 diabetes, on metformin, age between 18-55 yrs, male or female Exclusion Criteria: patients with type 1 diabetes, medically unstable, unacceptable clinical laboratory test results at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* double-dummy placebo tablets administered once-daily for 84-days<br>|
| Experimental: PF-04937319 - Dose 1<br> | Drug: PF-04937319 - 3mg<br>* PF-04937319 3mg administered as tablets once-daily for 84-days<br>|
| Experimental: PF-04937319 - Dose 2<br> | Drug: PF-04937319 - 20mg<br>* PF-04937319 20mg administered as tablets once-daily for 84-days<br>|
| Experimental: PF-04937319 - Dose 3<br> | Drug: PF-04937319 - 50mg<br>* PF-04937319 50mg administered as tablets once-daily for 84-days<br>|
| Experimental: PF-04937319 - Dose 4<br> | Drug: PF-04937319 - 100mg<br>* PF-04937319 100mg administered as tablets once-daily for 84-days<br>|
| Active Comparator: Sitagliptin<br> | Drug: Sitagliptin - 100mg<br>* Sitagliptin 100mg administered as tablets once-daily for 84-days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1C) at Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average glycemic control over prolonged periods of time. The normal range for the HbA1c test, was identified as less than (<) 6.5 percent (%) by the study-specific central laboratory used. Change from baseline in percentage of HbA1c in participants were reported. | Baseline (Day 1), Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1C) at Week 2, 4 and 8 | HbA1c is a form of hemoglobin which is measured primarily to identify the average glycemic control over prolonged periods of time. The normal range for the HbA1c test, was identified as <6.5 percent by the study-specific central laboratory used. Change from baseline in percentage of HbA1c in participants were reported. | Baseline(Day 1), Week 2, 4, 8 | 
| Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8, 12 and 14 |  | Baseline (Day 1), Week 1, 2, 4, 8, 12, 14 | 
| Percentage of Participants Achieving Less Than 6.5 Percent and Less Than 7 Percent Glycosylated Hemoglobin (HbA1c) Levels at Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average glycemic control over prolonged periods of time. The normal range for the HbA1c test, was identified as <6.5 percent by the study-specific central laboratory used and data are presented in categories of <6.5 percent and <7 percent. | Week 12 | 
| Number of Participants With Increase From Baseline Electrocardiogram (ECG)Data | Criteria for increase from baseline data: PR interval (percent change of greater than or equal to [>=] 25/50% [if baseline>200 then percent change of >25% counts; if baseline <=200 then percent change of >50% counts]; QRS complex (percent change of >=50%); QT Fridericia's correction (QTcF) interval (change of >=30 to <60 millisecond [msec], and change of >=60 msec). | Baseline (Day 1) up to Week 14 | 
| Number of Participants With Increase/Decrease From Baseline Vital Signs Data | Participants who met the criteria for increase or decrease in vital signs data were reported. Criteria for increase or decrease from baseline vital signs data: sitting systolic blood pressure (BP) of >=30 millimeter of mercury (mmHg); sitting diastolic BP of >=20 mmHg and pulse rate was based on investigator's discretion. | Baseline (Day 1) up to Week 14 | 
| 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 without regard to possibility of causal relationship. 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 14 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. | Baseline (Day 1) up to 14 days after last dose (up to 101 days) | 
| Percentage of Participants With at Least 1 Hypoglycemic Events (HAE) Episode | A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. HAE is defined as 1 of the given definitions: Characteristic symptoms of HAE with no home glucose monitoring performed where clinical picture included prompt resolution with food intake, subcutaneous glucagon, or intravenous glucose; or characteristic symptoms of HAE with home glucose monitoring measurement =< 70 milligram per deciliter (mg/dL) using ACCU-CHEK plasma-referenced home glucometers or =<74 mg/dL using International Federation of Clinical Chemistry (IFCC) referenced ACCU-CHEK or central laboratory glucometers; or any laboratory glucose value, meeting the following criterion with or without accompanying symptoms: =<49 mg/dL using ACCU-CHEK plasma-referenced home glucometers or =<53 mg/dL using IFCC referenced ACCU-CHEK or central laboratory glucometers. | Baseline (Day 1) up to Week 14 | 
| Number of Hypoglycemic Events (HAE) Episodes Per Participant | A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. Median number of events per participant was reported | Baseline (Day 1) up to Week 14 | 
| Change From Baseline in Body Weight at Week 2, 4, 8, 12 and 14 |  | Baseline (Day 1), Week 2, 4, 8 , 12 , 14 | 
| Number of Participants With Abnormal Laboratory Values | Hemoglobin,hematocrit,red blood cells(RBC) count:less than [<]0.8*lower limit of normal[LLN],platelets:<0.5*LLN/greater than [>]1.75*upper limit of normal [ULN],white blood cells(WBC):<0.6*LLN or >1.5*ULN,lymphocytes,total neutrophils:<0.8*LLN or >1.2*ULN, basophils,eosinophil,monocytes:>1.2*ULN;aspartate aminotransferase,alanine aminotransferase, alkaline phosphatase:>0.3*ULN,total protein,albumin:<0.8*LLN or >1.2*ULN;total bilirubin,direct bilirubin,indirect bilirubin:>1.5*ULN;triglycerides,cholesterol:>1.3*ULN, HDL:<0.8*LLN, LDL:>1.2*ULN,blood urea nitrogen,creatinine:>1.3*ULN,uric acid:>1.2*ULN;sodium: <0.95*LLN or >1.05*ULN,potassium,chloride,calcium,bicarbonate:<0.9*LLN or >1.1*ULN;creatine kinase:>2.0*ULN;glucose:<0.6*LLN or >1.5*ULN,urine WBC and RBC:>= 20/High Power Field [HPF]),urine epithelial cells (>=1 HPF),urine bacteria >20 high-powered field;qualitative urine glucose,urine blood to Hgb ratio (>=1);urine(protein,nitrite,mucus,leukocyte >=1 in urine dipstick test). | Baseline (Day 1) up to Week 14 | 

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