A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Omarigliptin; Placebo
Intervention description: Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly; Matching placebo to omarigliptin capsule or tablet administered orally once weekly
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 4202.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the cardiovascular (CV) safety profile of
      omarigliptin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is
      that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo
      and active comparators across the omarigliptin program with regard to the risk of developing
      a confirmed event in the primary CV composite endpoint.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed with type 2 diabetes mellitus

          -  Is on one of the following diabetes treatment regimens that is stable for at least 12
             weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C
             range for that treatment regimen:

               1. A1C >= 6.5% and <= 10.0% (>=48 mmol/mol and <=86 mmol/mol) on: (a) diet or
                  exercise alone (not on antihyperglycemic agent [AHA] for >= 12 weeks) OR (b)
                  monotherapy with metformin (MF), pioglitazone (PIO) or an alpha-glucosidase
                  inhibitor (AGI) or a sodium-glucose cotransporter inhibitor (SGLT2i) OR (c) dual
                  combination therapy with MF, PIO, AGI or SGLT2i OR

               2. A1C >= 7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on (a) monotherapy with
                  a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea
                  or a meglitinide and MF, PIO, AGI, or SGLT2i OR

               3. A1C >=7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on one of the following
                  insulin regimens (with or without metformin): (a) basal insulin (e.g.; insulin
                  glargine, insulin detemir, NPH insulin, degludec) OR (b) prandial insulin (e.g.
                  regular, aspart, lispro, glulisine) OR (c) basal/prandial insulin regimen
                  consisting of multiple dose insulin injections of basal and prandial insulin or
                  the use of pre-mixed insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog
                  75/25®, or Humulin 70/30®

          -  Pre-existing vascular disease (coronary artery disease, ischemic cerebrovascular
             disease, atherosclerotic peripheral artery disease)

          -  (1) Male; (2) female not of reproductive potential; or (3) female of reproductive
             potential who agrees to remain abstinent or use alone or in conjunction with their
             partner 2 methods of 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

          -  Treated with rosiglitazone, a dipeptidyl peptidase-IV (DPP-4) inhibitor, or a
             glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to study
             participation or previously treated with omarigliptin

          -  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

          -  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

          -  Human immunodeficiency virus (HIV) as assessed by medical history

          -  New or worsening coronary heart disease, congestive heart failure, myocardial
             infarction, unstable angina, coronary artery intervention, stroke, or transient
             ischemic neurological disorder within the past 3 months

          -  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

          -  Clinically important hematological disorder (such as aplastic anemia,
             myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

          -  Pregnant or breast feeding, or is expecting to conceive or donate eggs during the
             trial, including 21 days following the last dose of study drug