Type 2 Diabetes Mellitus MedDRA version: 14.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Pfizer Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Males and/or females of non-childbearing potential between the ages of 18 (or 21 based on country-specific age of consent) and 70 years, inclusive, at screening. 2. Subjects who have been on a stable dose of metformin either alone or in combination with an acceptable OAD agent (other than metformin) for their T2DM for at least 6 weeks prior to V1. • Subjects on an acceptable OAD medication (other than metformin) must be willing to discontinue this medication starting at V2 and for duration of the study (ie, until the follow-up visit V10). 3. HbA1c at Screen (as assessed by study-specific central laboratory) meeting one of the following criteria based on prior background OAD agent: • Metformin monotherapy ? 7.0 - 11.0%, inclusive • Metformin + acceptable OAD agent? 6.5 - 9.5%, inclusive* * upper limit was chosen so that subjects would have HbA1c =11.0% at randomization following withdrawal of the acceptable OAD medication based on expected rise in HbA1c post discontinuation. 4. BMI of =22.5 kg/m2 and =45.5 kg/m2, at screening. 5. 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. 6. Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures, including the ability to perform self tests of blood sugar at least once daily and have the capacity to store the study drug at 2-8 degrees C for the duration 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 245 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. Diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes; 2. Fasting plasma glucose levels >270 mg/dL (ie, 14.98 mmol/L), at V1 (as assessed by study-specific central laboratory) confirmed by a single repeat, if deemed necessary; 3. History or evidence of diabetic complications with clinically significant symptomatic or known, end-organ damage such as: • Proliferative retinopathy and/or macular edema; or • Diabetic neuropathy complicated by neuropathic ulcers; or • Creatinine clearance =60 mL/min based on Cockcroft Gault equation using serum creatinine measured at screening, confirmed via a single repeat, if deemed necessary [See below]: • Males ? [(140 - age in years) x total body weight (in kg)] divided by [72 x serum creatinine (in mg/dL)]; • Females ? 0.85 x calculation for males. 4. Recent (ie, within 6 months prior to screening) evidence or medical history of unstable concurrent disease such as clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or clinically significant allergic disease (including any drug allergies, but excluding treated and untreated seasonal allergies at the time of dosing); 5. History of myocardial infarction, unstable angina, coronary revascularization, stroke or transient ischemic attack within 6 months of screening; 6. Past medical history of pancreatitis; 7. Persistent, severe, uncontrolled hypertension; for example: sitting systolic blood pressure =180 mm Hg and/or diastolic blood pressure =105 mm Hg after at least 5-minutes seated rest at screening, confirmed via 1 repeat if deemed necessary; 8. At screening, 12-lead electrocardiogram (ECG) demonstrating QTc interval >470 msec, confirmed by a single repeat, if deemed necessary; 9. Subjects with any of the following findings in clinical laboratory tests at screening as assessed by study specific central laboratory confirmed by a single repeat, if deemed necessary: • C peptide concentration of ULN; • Those with history of Gilbert's syndrome are eligible for this study provided direct bilirubin is =ULN. 10. The following therapeutic agents are prohibited for the duration of the study. These medications are not to be used from the time of the start of the placebo baseline period (V3) to the completion of the dosing period (V9). • Chronic oral or parenteral corticosteroids (eg, prednisone, dexamethasone, methylprednisolone or hydrocortisone) at any dose. Intercurrent steroid treatment may be administered if treatment does not exceed one week. Note that inhaled and topical corticosteroids are permitted; • Orlistat, sibutramine, rimonabant, or other medications approved for weight loss; • Anti-psychotic medication including olanzapine, risperidone; • Drugs known to inhibit organic anion transport proteins (OATPs), including gemfibrozil, rifampin, cyclosporine, clarithromycin, and protease inhibitors (eg, lopinavir, ritonavir, indinavir). 11. The following diabetic agents are prohibited for the duration of the study. These medications are not to be used within 6 weeks prior to V1 to the completion of the study (V9). • Insulin; • Thiazolidi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the dose response of PF-04991532 administered twice daily over 12 weeks on HbA1c in adults with T2DM on stable doses of metformin.;Secondary Objective: • To characterize the dose responses of PF-04991532 administered twice daily and sitagliptin 100 mg administered once daily on fasting plasma glucose over 12 weeks in adults with T2DM on stable doses of metformin. • To evaluate the dose responses of PF-04991532 administered twice daily and sitagliptin 100 mg administered once daily over 12 weeks on body weight in adults with T2DM on stable doses of metformin. • To evaluate the safety and tolerability of a range of oral doses of PF-04991532 administered twice daily and sitagliptin 100 mg administered once daily, over 12 weeks in adults with T2DM on stable doses of metformin.;Primary end point(s): Change from baseline in HbA1c (%) at Week 12 (Day 84) as compared to placebo.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in fasting plasma glucose (mg/dL) at Weeks 1, 2, 4, 8 and 12. • Change from baseline in HbA1c at Weeks 1, 2, 4, and 8. • Proportion of subjects achieving HbA1c <7%, as well as the proportion achieving <6.5% at Week 12. • Change from baseline in body weight at Weeks 1, 2, 4, 8 and 12. • Proportion of subjects at Week 12 with body weight gain from baseline =1%. • Proportion of subjects at Week 12 with body weight loss from baseline =1%. • Proportion of subjects at Week 12 with body weight gain from baseline =2%. • Proportion of subjects at Week 12 with body weight loss from baseline =2%. • Assessment of clinical laboratory tests, 12 lead ECGs, vital signs, adverse events (AEs), as well as serious AEs (SAEs) and including episodes of hypoglycemic adverse events (HAEs). ;Timepoint(s) of evaluation of this end point: Timepoints are defined within the Secondary end points | — |
Countries
Bulgaria, Hungary, India, Mexico, Poland, Serbia, Slovakia, Taiwan
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc
Outcome results
None listed