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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: PF-04937319 - 3mg; Drug: PF-04937319 - 20mg; Drug: PF-04937319 - 50mg; Drug: PF-04937319 - 100mg; Drug: Sitagliptin - 100mg

• Study Type: Interventional
• Enrollment (Actual): 345
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Balatonfured, Hungary, 8230
    • DRC Kft.
  • Bekescsaba, Hungary, 5600
    • Dr. Rethy Pal Korhaz-Rendelointezet
  • Budapest, Hungary, 1036
    • Qualiclinic Kft.
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
  • Debrecen, Hungary, 4043
    • Kenezy Korhaz Rendelointezet Egeszsegugyi Nonprofit Kft.
  • Gyor, Hungary, 9023
    • Petz Aladar Megyei Oktato Korhaz
  • Polgar, Hungary, 4090
    • Polgar es Tersege Egeszsegugyi Kozpont Nonprofit Zrt.
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Kórház
• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 007
      • Bhatia Hospital
    • Mumbai, Maharashtra, India, 400 012
      • Seth G S Medical College & KEM Hospital, Dept of Endocrinology,
    • Pune, Maharashtra, India, 411001
      • Jehangir Clinical Development Centre Pvt. Ltd.
  • Rajasthan
    • Jaipur, Rajasthan, India, 302001
      • S.R. Kalla Memorial Gastro and General Hospital
• Philippines
  • Cebu City, Philippines, 6000
    • Vicente Sotto Memorial Medical Center
  • Marikina City, Philippines, 1810
    • Institute for Studies on Diabetes Foundation Inc.
  • Pasig City, Philippines, 1605
    • The Medical City
• Romania
  • Bucuresti, Romania, 011234
    • Institutul National de Diabet, Nutritie si Boli Metabolice Prof. Dr. N. Paulescu
  • Bucuresti, Romania, 020475
    • Institutul National de Diabet, Nutritie si Boli Metabolice Prof. Dr. N. Paulescu
  • Jud. Cluj
    • Cluj-Napoca, Jud. Cluj, Romania, 400006
      • Spitalul Clinic Judetean de Urgenta Cluj-Napoca
• Slovakia
  • Bratislava, Slovakia, 831 01
    • Metabolicke centrum MUDr. Katariny Raslovej, s.r.o.
  • Bratislava, Slovakia, 851 01
    • Medispektrum Plus, s.r.o.
  • Lucenec, Slovakia, 984 01
    • IN-DIA, s.r.o.
  • Nitra, Slovakia, 949 01
    • MUDr. Zuzana Ochodnicka, Interna diabetologicka ambulancia, s.r.o.
  • Nove Mesto nad Vahom, Slovakia, 915 01
    • NOEMIS, s.r.o.
  • Presov, Slovakia, 080 01
    • DIABETOL, s.r.o.
  • Trebisov, Slovakia, 075 01
    • Areteus, s.r.o.
  • Trencin, Slovakia, 911 01
    • Diabetes centrum, s.r.o.
• South Africa
  • Durban, South Africa, 4091
    • Randles Road Medical Centre
  • Moloto, South Africa, 1022
    • AA Mahomed Medical Centre
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Bloemfontein Medi-Clinic
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1829
      • Dr DR Lakha's Practice
    • Midrand, Gauteng, South Africa, 1685
      • Midrand Medical Centre
    • Pretoria, Gauteng, South Africa, 0083
      • Medi-Clinic Heart Hospital
    • Waverley, Gauteng, South Africa, 2090
      • Dr Bhana
  • Northern Cape
    • Kimberley, Northern Cape, South Africa, 8301
      • Dr JH Mynhardt
• Taiwan
  • Changhua City, Taiwan, 500
    • Changhua Christian Hospital
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital, Division of Endocrinology and Metabolism
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital, Division of Metabolism and Endocrinology
  • Tainan, Taiwan, 710
    • Chi Mei Medical Center
• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Florida
    • Belleview, Florida, United States, 34420
      • The Family Doctors of Belleview
    • Miami, Florida, United States, 33135
      • Swiss Medical Research
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
  • Georgia
    • Conyers, Georgia, United States, 30094
      • Rockdale Medical Research Associates
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Kentucky
    • Mount Sterling, Kentucky, United States, 40353
      • Central Kentucky Research Associates, Inc.
    • Mount Sterling, Kentucky, United States, 40353
      • Mount Sterling Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • The Office of Dr. Matthew S. Barton, MD
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • TKL Research, Inc.
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research, LLC
  • Ohio
    • Kettering, Ohio, United States, 45429
      • PriMed Clinical Research
    • Kettering, Ohio, United States, 45429
      • PriMed Physicians
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South, LLC
    • Charleston, South Carolina, United States, 29407
      • Newton Family Medicine
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Center for Clinical Research
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Plano, Texas, United States, 75024
      • Plano Primary Care Clinic
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions, Inc.
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; double-dummy placebo tablets administered once-daily for 84-days
Active Comparator: Sitagliptin	Drug: Sitagliptin - 100mg; Sitagliptin 100mg administered as tablets once-daily for 84-days
Experimental: PF-04937319 - Dose 1	Drug: PF-04937319 - 3mg; PF-04937319 3mg administered as tablets once-daily for 84-days
Experimental: PF-04937319 - Dose 2	Drug: PF-04937319 - 20mg; PF-04937319 20mg administered as tablets once-daily for 84-days
Experimental: PF-04937319 - Dose 3	Drug: PF-04937319 - 50mg; PF-04937319 50mg administered as tablets once-daily for 84-days
Experimental: PF-04937319 - Dose 4	Drug: PF-04937319 - 100mg; PF-04937319 100mg administered as tablets 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 in participants were reported.	Baseline (Day 1), Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 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

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: November 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 21, 2011

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: type 2 diabetes mellitus; 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: B1621007; 2011-004002-25 (EudraCT Number)