Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin; Sitagliptin; Placebo to Ertugliflozin; Placebo to Sitagliptin; Glimepiride
Intervention description: Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks.; Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.; Matching placebo to ertugliflozin administered orally, once daily for 26 weeks.; Matching placebo to sitagliptin administered orally, once daily for 26 weeks.; Open-label glimepiride rescue therapy will be initiated at 1 or 2 mg/day and may be titrated to the maximum labeled dose or maximum tolerated dose (if lower than labeled dose), as considered appropriate by the investigator, based on blood glucose measurements and in accordance with the local, approved label.
Intervention MeSH terms: Sitagliptin Phosphate; Glimepiride; Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 291.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study to evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in
      combination with sitagliptin in the treatment of participants with Type 2 diabetes mellitus
      (T2DM) with inadequate glycemic control on diet and exercise. The primary hypothesis of the
      study is that ertugliflozin plus sitagliptin is more effective in lowering of hemoglobin A1C
      (HbA1C) than placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus as per American Diabetes Association guidelines

          -  Not on antihyperglycemic agent (AHA) >=8 weeks with a Visit 1/Screening HbA1C >=8.0%
             and <=10.5% (>=64 mmol/mol and <=91 mmol/mol) OR on single allowable AHA (allowable
             AHAs prior to screening are: metformin, α-glucosidase inhibitors, sulfonylureas and
             glinides) with a Visit 1/Screening HbA1C >=7.5% and <=10.0% (>=58 mmol/mol and <=86
             mmol/mol) OR on low-dose dual combination therapy (≤50% of maximum labeled dose of an
             AHA) with allowable AHAs with a Visit 1/Screening HbA1C >=7.5% and <=10.0% (>=58
             mmol/mol and <=86 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 (or have their partner agree to) remain
             abstinent from heterosexual activity or to use 2 acceptable combinations of
             contraception.

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or diabetic 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

          -  A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2)
             inhibitor or sitagliptin

          -  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
             [i.e., <=7 days] during concomitant illness or other stress), other injectable
             anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or
             rosiglitazone, other sodium glucose co-transporter 2 (SGLT2) inhibitors,
             dipeptidyl-peptidase 4 inhibitors (DPP-4 inhibitors), bromocriptine (Cycloset™),
             colesevelam (Welchol™), any other AHA with the exception of the protocol-approved
             agents

          -  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 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

          -  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

          -  A known history of human immunodeficiency virus (HIV)

          -  A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a
             clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative
             or myelodysplastic syndromes, thrombocytopenia)

          -  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

          -  Any clinically significant malabsorption condition

          -  Current treatment for hyperthyroidism

          -  On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior
             study start

          -  On a previous clinical study with ertugliflozin

          -  Participated in other studies involving investigational drug(s) 30 days prior to study
             start

          -  Surgical procedure within 6 weeks prior to study start or major surgery planned during
             the trial

          -  Positive urine pregnancy test

          -  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

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
             engages in binge drinking

          -  Donated blood or blood products within 6 weeks of study start.