A Study of Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus With Chronic Kidney Disease or Kidney Failure on Dialysis (MK-3102-019)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Omarigliptin; Placebo to omarigliptin; Glipizide; Placebo to glipizide; Insulin
Intervention description: Participants with moderate renal insufficiency will receive one omarigliptin 25 mg capsule orally once a week; participants with severe renal insufficiency or end stage renal disease will receive one omarigliptin 12.5 mg capsule orally once a week; Matching placebo to omarigliptin capsule administered orally once a week; Phase A: Participants may receive open-label glipizide as rescue therapy up to Week 24 of the study. Phase B: Participants who received placebo to omarigliptin during Phase A and are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study Week 1 through Week 24) will receive glipizide capsule(s) 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).; Matching placebo to glipizide daily; Participants on insulin therapy at screening will continue insulin therapy during the study. Insulin glargine therapy may be administered as rescue therapy as determined by the investigator.
Intervention MeSH terms: Glipizide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 213.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy and safety of omarigliptin in
      participants with type 2 diabetes mellitus and moderate or severe chronic renal insufficiency
      or end stage renal disease on dialysis with inadequate glycemic control. The primary
      hypothesis of the study is that omarigliptin compared to placebo produces greater reduction
      in glycosylated hemoglobin (A1C) after 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus and be at least 30 years of age

          -  Moderate or severe chronic renal insufficiency or end stage renal disease on dialysis

          -  Meet one of the following criteria:

               1. is currently not on an antihyperglycemic agent (AHA) and has A1C >=7% and <=10%
                  at screening

               2. is currently on a single oral AHA or low-dose dual oral combination AHA and has
                  A1C >=6.5% and <=9% at screening

               3. is currently on a stable insulin regimen (>= 15 U/day) for >= 10 weeks, with no
                  oral AHA, and has A1C >=7.5% and <=10% and FPG >130 mg/dL at screening

          -  (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 28
             days after the last dose of study drug

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus or a history of ketoacidosis

          -  Treated with any incretin mimetic or thiazolidinedione (TZD) within 12 weeks prior to
             screening or with omarigliptin at any time prior to study participation

          -  History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor

          -  History of intolerance or hypersensitivity to glipizide or insulin glargine or any
             contraindication to glipizide or insulin glargine

          -  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

          -  Undergone a surgical procedure within 4 weeks prior to screening or has planned major
             surgery during the trial

          -  On or likely to require treatment for >=2 consecutive weeks or repeated courses of
             corticosteroids (note: inhaled, nasal or topical corticosteroids are permitted)

          -  Currently being treated for hyperthyroidism or is on thyroid replacement therapy and
             has not been on a stable dose for at least 6 weeks

          -  If on dialysis, does not regularly adhere to dialysis schedule

          -  Diagnosis of congestive heart failure with New York Heart Association (NYHA) Class IV

          -  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)

          -  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

          -  Poorly controlled hypertension

          -  Severe active peripheral vascular disease

          -  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)

          -  Positive pregnancy test

          -  Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the
             trial, including 28 days following the last dose of study drug

          -  User of recreational or illicit drugs or has had a recent history of drug abuse or
             routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or
             engages in binge drinking