Study To Understand Efficacy And Safety Of Investigational Agent (PF-04937319) Compared To Approved Agent (Glimepiride) In Patients With Diabetes On Metformin

A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-ranging, Parallel Group Study To Evaluate Safety And Efficacy Of Pf-04937319 And Glimepiride In Adult Patients With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin

This is a study to understand efficacy and safety of investigational agent (PF-04937319) compared to approved agent (glimepiride) in patients with diabetes on metformin

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: PF-04937319 10 mg; Drug: PF-04937319 50 mg; Drug: PF-04937319 100 mg; Drug: Glimepiride

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Byala, Bulgaria, 7100
    • MBAL Yulia Vrevska - Byala, Otdelenie po vatreshni bolesti
  • Ruse, Bulgaria, 7002
    • MBAL - Ruse AD, Vtoro otdelenie po vatreshni bolesti
  • Sevlievo, Bulgaria, 5400
    • DKTs Akta Medika, Kabinet po endokrinologia
  • Sofia, Bulgaria, 1431
    • UMBAL Aleksandrovska, Klinika po endokrinologia i bolesti na obmyanata
  • Sofia, Bulgaria, 1606
    • VMA - MBAL - Sofia, Klinika po endokrinologia i bolesti na obmyanata
  • Stara Zagora, Bulgaria, 6003
    • UMBAL Stara Zagora, Klinika po endokrinologia i bolesti na obmyanata
• Canada
  • Quebec, Canada, G3K 2P8
    • Alpha Recherche Clinique
  • British Columbia
    • Langley, British Columbia, Canada, V3A 4H9
      • Glover Medical Clinic
    • Surrey, British Columbia, Canada, V3S 2N6
      • Ocean West Research Clinic Inc.
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 4W3
      • Rivergrove Medical Clinic
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • Strathroy, Ontario, Canada, N7G 1Y7
      • DCTM CLinical Trials Group Ltd.
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research
  • Quebec
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Pro-Recherche
    • Terrebonne, Quebec, Canada, J6V 1S8
      • Centre de cardiologie et de Recherche Clinique Pierre-Le Gardeur
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Dr. Kenessey Albert Korhaz-Rendelointezet/Belgyogyaszat
  • Budapest, Hungary, 1036
    • Synexus Magyarorszag Kft.
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem/I. sz. Belgyogyaszati Klinika
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Korhaz/II. Belgyogyaszati Osztaly
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560060
      • BGS Global Hospital
  • Maharashtra
    • Pune, Maharashtra, India, 411 004
      • Deenanath Mangeshkar Hospital & Research Centre
    • Pune, Maharashtra, India, 411 011
      • Diabetes Unit, K.E.M. Hospital Research Centre
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
  • Moldava Nad Bodvou, Slovakia, 045 01
    • Interna A Diabetologicka Ambulancia
  • Nove Zamky, Slovakia, 940 01
    • FUNKYSTUFF, s.r.o.
  • Pezinok, Slovakia, 902 01
    • MEDIAB, s.r.o.
  • Zilina, Slovakia, 010 01
    • MEDIVASA, s.r.o.
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 110
    • Taipei Medical University Hospital
• United States
  • California
    • Roseville, California, United States, 95661
      • Sierra Clinical Research
    • San Diego, California, United States, 92103
      • California Research Foundation
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Bradenton, Florida, United States, 34208
      • Meridien Research
    • Pembroke Pines, Florida, United States, 33027
      • South Broward Research, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Massachusetts
    • Hyannis, Massachusetts, United States, 02601
      • Clinical Research Center of Cape Cod, Inc.
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Diabetes & Endocrinology Consultants, PC
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Community Research
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd.
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Holston Medical Group
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes and Endocrine Consultants
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research, Llc
    • Chattanooga, Tennessee, United States, 37404
      • Diagnostic Center
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • Austin, Texas, United States, 78728
      • Bristol Clinical Research, LLC
    • Bryan, Texas, United States, 77802
      • DiscoveResearch, Inc.
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
    • Richmond, Virginia, United States, 23294
      • National Clinical Research - Richmond, Inc.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Advanced Healthcare, 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:

• Age 18-70 yrs, male and females, with T2DM, on metformin alone or in combination with 1 other oral agent

Exclusion Criteria:

• Subjects with recent cardiovascular events, those with evidence of diabetic complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glimepiride	Drug: Glimepiride; Combination of tablets and capsules, dose of up to 6 mg, a total of 3 pills/dose, administered once daily for 84-days
Placebo Comparator: Placebo; Placebo to match PF-04937319 and glimepiride	Drug: Placebo; Combination of tablets and capsules, a total of 3 pills/dose, administered once daily for 84-days
Experimental: PF-04937319 10 mg	Drug: PF-04937319 10 mg; Combination of tablets and capsules, dose of 10 mg, a total of 3 pills/dose, administered once daily for 84-days
Experimental: PF-04937319 50 mg	Drug: PF-04937319 50 mg; Combination of tablets and capsules, dose of 50 mg, a total of 3 pills/dose, administered once daily for 84-days
Experimental: PF-04937319 100 mg	Drug: PF-04937319 100 mg; Combination of tablets and capsules, dose of 100 mg, a total of 3 pills/dose, administered once daily for 84-days

What is the study measuring?

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 was 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, 6 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 less than 6.5 percent by the study-specific central laboratory used. Change from baseline in percentage of HbA1C was reported.	Baseline (Day 1), Week 2, 4, 6, 8
Change From Baseline in Fasting Plasma Glucose at Week 2, 4, 6, 8 and 12		Baseline (Day 1), Week 2, 4, 6, 8, 12
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 less than 6.5 percent by the study-specific central laboratory used and data are presented in categories of less than 6.5 percent and less than 7 percent.	Week 12
Number of Participants With Increase From Baseline Electrocardiogram (ECG) Data	Participants who met the criteria for increase from baseline in ECG data were reported. Criteria for increase from baseline data: PR interval (percent change of greater than or equal to [>=] 25/50% [if baseline value was >200 then percent change of >25% counts; if baseline value was <=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 of study treatment (up to 101 days)
Percentage of Participants With at Least 1 Hypoglycemic Events (HAE) Episode	A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. HAE was 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 was identified by characteristic symptoms or blood glucose levels. Median of 1 and 2 events per participant was reported.	Baseline (Day 1) up to Week 14
Time to Each Recurrent Hypoglycemic Events (HAE) Episode Per Participant	Median recurrence time was not to be calculated when less than 50% of the participants in a given arm experienced 1 or more HAEs.	Baseline (Day 1) up to Week 14
Change From Baseline in Body Weight at Week 2, 4, 6, 8, 12 and 14		Baseline (Day 1), Week 2, 4, 6, 8, 12, 14 (follow-up)
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Amin NB, Aggarwal N, Pall D, Paragh G, Denney WS, Le V, Riggs M, Calle RA. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9. doi: 10.1111/dom.12474. Epub 2015 May 11.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: T2DM; Phase 2; PF-04937319
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Glimepiride
• Other Study ID Numbers: B1621002; 2011-005206-30 (EudraCT Number)