Type 2 Diabetes Mellitus MedDRA version: 18.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects =18 years of age at the time of the initial Screening Visit (S1) with a diagnosis of T2DM in accordance with ADA guidelines.13 2. Subjects with no prior allowable oral AHA for =8 weeks prior to S1 with an HbA1c 7.0 10.5% (53-91 mmol/mol) at the initial Screening Visit (S1) or subjects on monotherapy with a single allowable oral AHA with an HbA1c 6.5-9.5% (48 80 mmol/mol) at the initial Screening Visit (S1). Subjects discontinuing an oral AHA at Screening Visit (S2) should remain off the oral AHA for =8 weeks prior to Screening Visit (S3) and will require an HbA1c of 7.0-10.5% (53-91 mmol/mol) at Screening Visit (S3) in order to be randomized. 3. Subjects on a single allowable oral AHA must be willing to discontinue this medication starting at Screening Visit (S2) and remain off this medication for the duration of the trial. Allowable oral AHAs for discontinuation are metformin, sulfonylureas, DPP-4 inhibitors, glinides or alpha-glucosidase inhibitors. 4. Body Mass Index (BMI) ?18.0 kg/m2. 5. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 6. In the investigator’s opinion, subjects are willing and likely able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 7. Subject meets one of the following criteria (a, b or c): a. is a male. b. is a female not of reproductive potential defined as one who (See Section 4.4.4.1 and 4.4.4.2 for reference on childbearing potential): 1. is postmenopausal defined as at least 12 months with no menses in women =45 years of age, or 2. has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening Visit (S1). c. is a female of reproductive potential and: 3. agrees to remain abstinent from heterosexual activity (if this form of birth control is accepted by local regulatory agencies and ethics review committees as the sole method of birth control), or 4. agrees to use (or have her partner use) acceptable contraception to prevent pregnancy while the subject is receiving investigational product and for 14 days after the last dose of investigational product. Two methods of contraception will be used to avoid pregnancy. Acceptable combinations of methods include: • Use of one of the following double-barrier methods: diaphragm with spermicide and a condom; cervical cap and a condom; or a contraceptive sponge and condom. • Use of hormonal contraception (any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent [including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous patch]) with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; vasectomy; or IUD. • Use of an IUD with one of the following: condom; diaphragm with spermicide; contraceptive sponge; vasectomy; or hormonal contracepti
Exclusion criteria
Exclusion criteria: 1. History of type 1 diabetes mellitus or a history of ketoacidosis or subject assessed by the investigator as possibly having type 1 diabetes confirmed with a C-peptide 160 mm Hg and/or diastolic blood pressure >90 mm Hg after at least a 5-minute seated rest at Screening Visit (S1), confirmed via 1 repeat triplicate set at Screening Visit (S1) if deemed necessary. For subjects with a confirmed mean triplicate value of sitting systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg at the S1 visit, the Investigator and/or treating physician is allowed to adjust background blood pressure medication(s) to improve blood pressure control in order for the subject to be re screened. 6. Subject has a clinically significant ECG abnormality at Screening Visit (S1) that requires further diagnostic evaluation or intervention (eg, new, clinically significant arrhythmia or a conduction disturbance). 7. Subject has active, obstructive uropathy or indwelling urinary catheter. 8. Subject has a history of malignancy =5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Note (1) A subject with a history of malignancy >5 years prior to signing informed consent should have no evidence of residual or recurrent disease. Note (2) A subject with any history of melanoma, leukemia, lymphoma, or renal cell carcinoma is excluded. 9. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking. Note (1): One alcoholic drink is defined as 5 oz (150 mL) of wine, or 12 oz (350 mL) of beer, or 1.5 oz (50 mL) of 80-proof liquor. Note (2): Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male), or 4 or more alcoholic drinks (female) in about 2 hours. 10. Any clinically significant malabsorption condition. 11. Meets any of the following categories: 12. Subject is on a weight-loss program and is not weight-stable. 13. Subject is on a weight-loss medication (eg, orlistat, phentermine/topiramate, lorcaserin) and is not weight-stable. 14. Subject is on other medications associated with weight changes (eg, anti-psychotic agents) and is not weight-stable. 15. Subject has undergone bariatric surgery >12 months prior to Visit 1/Screening and is not weight-stable. 16. Subject has undergone bariatric surgery within 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): • Change in HbA1c from Baseline to Week 26.;Timepoint(s) of evaluation of this end point: Assessment according to protocol; Main Objective: (1) Objective: At Week 26, to assess the effect on HbA1c of 15 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in HbA1c for 15 mg ertugliflozin is greater than that for placebo. (2) Objective: At Week 26, to assess the effect on HbA1c of 5 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in HbA1c for 5 mg ertugliflozin is greater than that for placebo. (3) Objective: To assess the safety and tolerability of ertugliflozin. ; Secondary Objective: (1) Objective: At Week 26, to assess the effect on fasting plasma glucose (FPG) of 15 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in FPG for 15 mg ertugliflozin is greater than that for placebo. (2) Objective: At Week 26, to assess the effect on FPG of 5 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in FPG for 5 mg ertugliflozin is greater than that for placebo. (3) Objective: At Week 26, to assess the effect on body weight of 15 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in body weight for 15 mg ertugliflozin is greater than that for placebo. (4) Objective: At Week 26, to assess the effect on body weight of 5 mg ertugliflozin as compared with placebo. Hypothesis: At Week 26, the mean reduction from baseline in body weight for 5 mg ertugliflozin is greater than that for placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from Baseline in FPG at Week 26. • Change from Baseline in body weight at Week 26. • Incidence of HbA1c <7% (53 mmol/mol) at Week 26. • Change from Baseline in 2-hour post-prandial plasma glucose at Week 26. • Change from Baseline in systolic blood pressure at Week 26. • Change from Baseline in diastolic blood pressure at Week 26. ;Timepoint(s) of evaluation of this end point: Assessment according to protocol | — |
Countries
Canada, Israel, Italy, Lithuania, Mexico, Romania, South Africa, United Kingdom, United States
Contacts
Public ContactSenior Director, Clinical Sciences
Pfizer Inc.
Outcome results
None listed