Phase 2 clinical trial to investigate the safety and how both PF-04937319 and sitigliptin work to control blood sugar, inadequately controlled on metformin, in people who have been diagnosed with Type 2 Diabetes within the past 5 years.

• Register: EUCTR
• Last refreshed on: 25 March 2013
• Main ID: EUCTR2011-004002-25-HU
• Date of registration: 17/11/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: Phase 2 clinical trial to investigate the safety and how both PF-04937319 and sitigliptin work to control blood sugar, inadequately controlled on metformin, in people who have been diagnosed with Type 2 Diabetes within the past 5 years.
• Scientific title: 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 - 12 WEEK POC IN T2DM WITH SITAGLIPTIN
• Date of first enrolment: 12/01/2012
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004002-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Dose-Ranging If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 6

Countries of recruitment

Hungary, India, Philippines, Romania, Serbia, Slovakia, South Africa, Taiwan, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects between the ages of 18 (or 21 based on country-specific age of consent) and 55 years, inclusive at screening
2. Females are permitted to be of childbearing as well as non-childbearing potential
3. Subjects with a diagnosis of T2DM with date of diagnosis within 5-years of date of consent for this study
4. Subjects on stable doses of metformin either alone or in combination with an acceptable oral anti-diabetic agent (with intent to discontinue agents other than metformin once deemed eligible)
5. HbA1C at screen of 7-11%, inclusive (those on metformin alone) and 6.5-9.5%, inclusive (those on metformin plus another agent)
6. Fasting plasma glucose < 270 mg/dL (ie, 15.04 mmol/L)
7. BMI of =18.5 kg/m2 and =45.4 kg/m2, and body weight >50 kg (110 lbs),
8. Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
9. Subjects willing and able to perform self test of blood sugars at least once daily, and maintain a diary
10. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Compliance (based on pill count) of <90% during baseline period, as assessed prior to randomization on Day 1 (V4).
2. Arm circumference >50 cm when measured at midpoint of the length of the upper arm
3. Recent [ie, within six (6) months prior to screening] evidence or medical history of unstable concurrent disease
4. Condition possibly affecting drug absorption
5. Diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes
6. Treatment with thiazolidinediones, or subcutaneously administered anti diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to Screening
7. Subjects who are non pharmacologically managed for their T2DM
8. Exclusion of selected concomitant medications prior to Screening
9. History or evidence of diabetic complications
10. History of myocardial infarction, unstable angina, coronary revascularization, stroke or transient ischemic attack within 6 months prior to screening
11. History of pancreatitis
12. Episode(s) of hypoglycemia of ‘severe’ intensity
13. Participation in any formal weight loss program, or fluctuation in body weight, or having received medications approved for weight loss
14. Clinically significant abnormalities in laboratory parameters
15. 12 lead electrocardiogram (ECG) demonstrating QTc interval >470 msec
16. Persistent severe, uncontrolled hypertension
17. Current medical history or current clinical evidence of congestive heart failure, NYHA (New York Heart Association) Functional Classification, Classes III IV
18. A positive urine drug test for illicit drugs
19. History of regular alcohol consumption
20. Participation in other studies involving administration of an investigational drug or device within 30 days
21. History of sensitivity or intolerance to PF-04937319 or sitagliptin
22. History of sensitivity to heparin or heparin-induced thrombocytopenia (if heparin is used to flush intravenous catheters used during OGTT)
23. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening
24. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the study
25. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Type 2 Diabetes Mellitus (T2DM)
MedDRA version: 14.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: Not Applicable
Product Code: PF-04937319
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
Current Sponsor code: PF-04937319
Other descriptive name: IUPAC: N,N-dimethyl-5-(2-methyl-6-(5-methylpyrazin-2-ylcarbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Not Applicable
Product Code: PF-04937319
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
Current Sponsor code: PF-04937319
Other descriptive name: IUPAC: N,N-dimethyl-5-(2-methyl-6-(5-methylpyrazin-2-ylcarbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Not Applicable
Product Code: PF-04937319
Pharmaceutical Form: Tablet
INN or Proposed INN: Not Applicable
Current Sponsor code: PF-04937319
Other descriptive name: IUPAC: N,N-dimethyl-5-(2-methyl-6-(5-methylpyrazin-2-ylcarbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Januvia®
Pharmaceutical Form: Tablet
CAS Number: 486460-32-6
Other descriptive name: sitagliptin phosphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To characterize the effect on additional parameters of glycemic control with a range of oral doses of PF-04937319 administered once daily over 12 weeks in adults with T2DM on stable doses of metformin.
• To evaluate safety and tolerability of a range of oral doses of PF-04937319 administered once daily over 12 weeks in adults with T2DM on stable doses of metformin.
• To characterize efficacy and safety/tolerability of a 100 mg once daily dose of sitagliptin administered over 12 weeks in adults with T2DM on stable doses of metformin.

Timepoint(s) of evaluation of this end point: HbA1C, the primary endpoint will be evaluated at baseline (Day 1 predose), Day 28, 56 and 84, and 1-2 weeks post last dose

Primary end point(s): The comparison of interest following 12 weeks of dosing with a range of oral doses of PF-04937319 administered once daily is change from baseline in HbA1C (%) – Day 84 minus baseline (ie, Day 1) as compared to placebo.
• HbA1C change from baseline on Days 14, 28 and 56 will also be included and reported in the primary analysis model.

Main Objective: To evaluate the dose-response of PF-04937319, administered once daily over 12 weeks in adults with T2DM on stable doses of metformin, on glycemic control.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Change in fasting plasma glucose will be evaluated at baseline, Day 14, 28, 56, 84 and 1-2 weeks post last dose
Proportion of subjects achieving HbA1C <7% and <6.5% on Day 84Safety and tolerability – including 12-lead ECGs, vitals, AEs and SAEs, and clinical laboratory tests will be evaluated over the 84 days of dosing as well as 1-2 weeks post last dose – for both PF-04937319 and sitagliptin

Secondary end point(s): 1. Efficacy-related Endpoints
• Change from baseline in fasting plasma glucose (mg/dL) on Days 7, 14, 28, 56 and 84.
• Proportion of subjects achieving HbA1C <7% as well as <6.5% on Day 84.
2. Safety-related Endpoints
• Assessment of 12 lead ECGs, vital signs, AEs (as well as SAEs) including HAE, body weight, and laboratory tests (including lipid profile).
3. Sitagliptin-related Endpoints
• Efficacy and safety parameters as being assessed for PF-04937319.

Secondary ID(s)

B1621007

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017