Study to Evaluate the Safety and Efficacy of the Addition of Omarigliptin (MK-3102) Compared With the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin (MK-3102-026)
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Omarigliptin; Sitagliptin; Placebo to omarigliptin; Placebo to Sitagliptin; Open-label Metformin; Open-label Glimepiride
Intervention description: Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks; Sitagliptin 100 mg oral tablet once a day for 24 weeks; Placebo to omarigliptin 25 mg oral capsule once a week for 24 weeks; Placebo to sitagliptin 100 mg oral tablet once a day for 24 weeks; Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day; Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Glimepiride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 642.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Glimepiride; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions

Summary:

      This is a non-inferiority study comparing omarigliptin with sitagliptin in participants with
      type 2 diabetes mellitus (T2DM) with inadequate glycemic control on metformin therapy. The
      primary hypothesis is that after 24 weeks, the mean change from baseline in hemoglobin A1c
      (A1C) in participants treated with omarigliptin is non-inferior to that in participants
      treated with sitagliptin. There will be a 2-week run-in period with placebo + metformin prior
      to the double-blind treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus

          -  Currently on a stable dose of metformin monotherapy (≥1500 mg per day) for at least 12
             weeks prior to study participation

          -  Male, or female who is not of reproductive potential or if of reproductive potential
             agrees to abstain from heterosexual activity or use (or have their partner use)
             acceptable contraception to prevent pregnancy during the study and for 21 days after
             the last dose of study drug

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or a history of ketoacidosis

          -  Has been treated with any antihyperglycemic agent (AHA) other than the
             protocol-required metformin within 12 weeks prior to study participation or with
             omarigliptin at any time prior to signing informed consent

          -  History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor

          -  Is currently participating in, or has participated in, a trial in which the
             participant received an investigational compound or used an investigational device
             within the prior 12 weeks of signing the informed consent or is not willing to refrain
             from participating in any other trial

          -  History of intolerance, hypersensitivity, or any other contraindication to metformin
             or sitagliptin

          -  Is on a weight loss program and is not in the maintenance phase or has been on a
             weight loss medication in the past 6 months or has undergone bariatric surgery within
             12 months prior to study participation

          -  Has undergone a surgical procedure within 4 weeks of study participation or has
             planned major surgery during the study

          -  Is on or likely to require treatment ≥14 consecutive days or repeated courses of
             corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

          -  Currently being treated for hyperthyroidism or is on thyroid hormone replacement
             therapy and has not been on a stable dose for at least 6 weeks

          -  Is expecting to undergo hormonal therapy in preparation to donate eggs during the
             period of the trial, including 21 days after the last dose of trial medication

          -  History of active liver disease (other than non-alcoholic steatosis) including chronic
             active hepatitis B or C, primary biliary cirrhosis, or symptomatic gall bladder
             disease

          -  Human immunodeficiency virus (HIV)

          -  New or worsening signs or symptoms of coronary heart disease or congestive heart
             failure within the past 3 months, or myocardial infarction, unstable angina, coronary
             artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or
             transient ischemic attacks in the past 3 months

          -  Poorly controlled hypertension

          -  History of malignancy ≤5 years prior to study participation, except for adequately
             treated basal cell or squamous cell skin cancer or in situ cervical cancer

          -  Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic
             syndromes, thrombocytopenia)

          -  Positive urine pregnancy test

          -  Pregnant or breastfeeding, or is expecting to conceive during the study including 21
             days following the last dose of blinded study drug

          -  User of recreational or illicit drugs or has had a recent history of drug abuse

          -  Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or
             engages in binge drinking

          -  Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study
             participation, or intends to donate blood products within the projected duration of
             the trial or has received, or is anticipated to receive, blood products within 12
             weeks of study participation or within the projected duration of the trial