A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin 5 mg; Ertugliflozin 15 mg; Placebo matching ertugliflozin; Metformin; Glimepiride
Intervention description: Ertugliflozin 5 mg oral tablet taken once daily; Ertugliflozin 15 mg (5-mg and 10-mg tablets) oral taken once daily; Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily; Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.; Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Intervention MeSH terms: Metformin; Glimepiride; Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Sponsor was masked.
Enrollment: 506.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study to evaluate the efficacy and safety of the addition of ertugliflozin to
      metformin monotherapy in Asian participants with Type 2 diabetes mellitis (T2DM) who have
      inadequate glycemic control on metformin monotherapy. The primary hypothesis is that the mean
      reduction from baseline in HbA1C for 15 mg and 5 mg ertugliflozin (tested sequentially) is
      greater than for placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Asian participants ≥18 years of age at the time of initial Screening.

          -  Type 2 diabetes mellitus as per American Diabetes Association guidelines.

          -  Metformin monotherapy (≥1500 mg/day) with an initial Screening A1C of 7.0-10.5% (53-91
             mmol/mol) OR metformin monotherapy (<1500 mg/day) with an initial Screening A1C of
             7.5-11.0% (58-97 mmol/mol) OR dual combination therapy with metformin + sulfonylurea,
             dipeptidyl peptidase-4 (DDP-4) inhibitor, meglitinide, or alpha-glucosidase inhibitor
             with an initial Screening A1C of 6.5-9.5% (48-80 mmol/mol).

          -  Body mass index (BMI) ≥18.0 kg/m^2.

          -  Male or female not of reproductive potential.

          -  Female of reproductive potential who agrees to remain abstinent from heterosexual
             activity or to use 2 acceptable combinations of contraception.

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or a history of ketoacidosis.

          -  History of other specific types of diabetes (e.g., genetic syndromes, secondary
             pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and
             post-organ transplant.)

          -  History of myocardial infarction, unstable angina, arterial revascularization, stroke,
             transient ischemic attack, or New York Heart Association (NYHA) functional class
             III-IV heart failure within 3 months of study start.

          -  Mean value for triplicate screening sitting systolic blood pressure >160 mm Hg and/or
             diastolic blood pressure >90 mm Hg after at least a 5-minute seated rest at screening

          -  Active, obstructive uropathy or indwelling urinary catheter.

          -  History of malignancy ≤5 years prior to study start, except for adequately treated
             basal cell or squamous cell skin cancer or in situ cervical cancer.

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
             engages in binge drinking.

          -  Any clinically significant malabsorption condition.

          -  Is on a weight-loss program or weight-loss medication or other medication associated
             with weight changes and is not weight stable prior to study start.

          -  Has undergone bariatric surgery within the past 12 months or >12 months and is not
             weight stable prior to study start.

          -  A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2)
             inhibitor.

          -  On a previous clinical study with ertugliflozin.

          -  Is taking blood pressure or lipid altering medications that have not been on a stable
             dose for at least 4 weeks prior to study start.

          -  Current treatment for hyperthyroidism.

          -  Male participants with a serum creatinine >=1.3 mg/dL (>=115 mol/L) or female
             participants with a serum creatinine >=1.2 mg/dL (>=106 mol/L) or participants with an
             estimated glomerular filtration rate (eGFR) <55 mL/min/1.73m^2 according to the
             4-variable Modification of Diet in Renal Disease (MDRD) equation at screening.

          -  An aspartate transaminase (AST) or alanine transaminase (ALT) >2X the upper limit of
             normal (ULN) range at screening, or a total bilirubin >1.5 X the ULN unless the
             participant has a history of Gilbert's.

          -  On thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
             prior to study start.

          -  A medical history of active liver disease (other than non-alcoholic hepatic
             steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or
             symptomatic gallbladder disease.

          -  Has been treated with any of the following agents within 12 weeks of study start or
             during the pre-randomization period: Insulin of any type (except for short-term use
             during concomitant illness or other stress), other injectable anti-hyperglycemic
             agents (e.g., pramlintide, exenatide, liraglutide), another SGLT2 inhibitor,
             bromocriptine, colesevelam, rosiglitazone or pioglitazone, or any other AHA with the
             exception of the protocol-approved agents.

          -  Is on or likely to require treatment ≥14 consecutive days or repeated courses of
             pharmacologic doses of corticosteroids.

          -  Has undergone a surgical procedure within 6 weeks prior to study start or has planned
             major surgery during the study.

          -  Pregnant or breast-feeding, or planning to conceive during the trial, including 14
             days following the last dose of study medication.

          -  Planning to undergo hormonal therapy in preparation for egg donation during the trial,
             including 14 days following the last dose of study medication.

          -  Donated blood or blood products within 6 weeks of study start.

          -  Has Human Immunodeficiency Virus (HIV).

          -  Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells.

          -  Has clinically important hematological disorders (such as aplastic anemia,
             myeloproliferative or myelodyplastic syndromes, thrombocytopenia.)