PHASE 2 CLINICAL TRIAL TO EVALUATE SAFETY AND EFFICACY OF PF-04937319 AND GLIMEPIRIDE IN ADULT PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMI

• Conditions: Type 2 Diabetes Mellitus (T2DM); MedDRA version: 14.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2011-005206-30-SK
• Lead Sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-11
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Male or female subjects between the ages of 18 (or the minimum country specific age of consent if > 18) and 70 years, inclusive at screening (V1)
• Subjects of childbearing potential must agree to use a highly effective method of contraception. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
• Female subjects may be of childbearing potential but must not be pregnant, breastfeeding, or planning to become pregnant for the duration of their participation in this study and within 28 days following last dose of assigned treatment.
• In female subjects, serum ß hCG level, confirmed via a single repeat if deemed necessary, must be within the central laboratory’s reference range for non-pregnant state.
• Female subjects may be deemed of non childbearing potential if one of the following criteria are met, at screening (V1):
• Have undergone hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure;
• Are medically confirmed to be post menopausal (eg, cessation of regular menses for =12 months with no alternative pathological or physiological cause);
• Serum FSH level, confirmed via a single repeat if deemed necessary, within the central laboratory’s reference range for postmenopausal state.
2. Subjects diagnosed, by a medical professional, with T2DM in accordance with the ADA guidelines.
3. Subjects who have been on a stable dose of metformin either alone or in combination with another oral anti-diabetic agent (excluding pioglitazone and rosiglitazone) for their T2DM for at least 6 weeks prior to V1.
4. Subjects on an oral anti diabetic agent 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).
5. HbA1C at Screen (ie, V1), as assessed by study specific central laboratory using a method that is National Glycohemoglobin Standardization Program (NGSP) certified and standardized to the Diabetes Control and Complications Trial (DCCT) assay, meeting one of the following criteria based on prior background anti-diabetic agents:
• Metformin monotherapy ?7.0 11.0%, inclusive;
• Metformin plus acceptable OAD ?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 based on expected rise in HbA1C post discontinuation.
6. Fasting plasma glucose levels <270 mg/dL (ie, 15.04 mmol/L), at screening, (as assessed by study-specific central laboratory) confirmed by a single repeat, if deemed necessary.
7. BMI of =18.5 kg/m2 and =45.4 kg/m2, and body weight >50 kg (110 lbs), at screening (V1).
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, as outlined in this protocol.
9. Subjects must be willing and able to perform self test of blood sugars at least once daily, and maintain a diary, for the duration of participation in the study.
10. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally

Exclusion Criteria

Subjects presenting with any of the following will not be included in the study:
1. Compliance (based on pill count) of <90% during baseline period, as assessed prior to randomization on Day 1 (V4).
2. Subjects with an 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 such as: documented evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal (including severe gastroparesis), cardiovascular, hepatic, psychiatric, neurologic, or clinically significant allergic disease (including any drug allergies, but excluding treated and untreated seasonal allergies at time of dosing).
4. Any condition possibly affecting drug absorption (eg, gastrectomy or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency).
5. Diagnosis of Type 1 diabetes mellitus or secondary forms of diabetes.
6. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to V1.
7. Subjects who are non pharmacologically managed for their T2DM (ie, treatment naïve).
8. Treatment with certain class of medications within a pre-specified interval prior to Screening (V1) and for duration of participation in this study:
9. 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.
• Macroalbuminuria defined as UACR =300 µg albumin per mg of creatinine (ie, 33.9 mg/mmol) in spot urine collection, at screening, confirmed via a single repeat, if deemed necessary.
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 HAE of ‘severe’ intensity prior to screening (V1); either:
• =1 in the previous 3 months; or
• =2 in the previous 6 months.
13. Participation in any formal weight loss program, or fluctuation of >5% in body weight, or having received medications approved for weight loss within 3 months prior to screening.
14. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening (ie, V1) as assessed by study specific central laboratory confirmed by a single repeat, if deemed necessary:
• C peptide concentration of <0.8 ng/mL (267 pmol/L);
• Fasting serum triglycerides =400 mg/dL (ie, 4.52 mmol/L);
• AST/SGOT or ALT/SGPT =2x ULN;
• Total bilirubin =1.5 x ULN and direct bilirubin > ULN; those with history of Gilbert's syndrome are eligible for this study provided direct bilirubin is = ULN.
15. At screening/V1, 12 lead electrocardiogram (ECG) demonstrating QTc interval >470 msec, following =10 minute supine rest, confirmed by a single repeat, if deemed necessary.
16. Persistent severe, uncontrolled hypertension; for example: seated systolic blood pressu

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified