| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 2 Diabetes Mellitus (T2DM) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Type 2 Diabetes Mellitus (T2DM) |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
• 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.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 |
|
| E.4 | Principal 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 |
|
| E.5 End points |
| E.5.1 | 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.
|
|
| E.5.1.1 | 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
|
|
| E.5.2 | 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. |
|
| E.5.2.1 | 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
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Hungary |
| India |
| Philippines |
| Romania |
| Serbia |
| Slovakia |
| South Africa |
| Taiwan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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