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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo to glipizide; Drug: Placebo to omarigliptin; Drug: Glipizide; Biological: Insulin; Drug: Omarigliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01698775

2012-002332-85 (EudraCT Number)

3102-019

Details and patient eligibility

About

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.

Enrollment: 213 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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213 participants in 2 patient groups

Omarigliptin (Phase A) → Omarigliptin (Phase B)

Experimental group

Description:

Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who 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 matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).

Treatment:

Drug: Placebo to glipizide

Biological: Insulin

Drug: Omarigliptin

Drug: Glipizide

Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

Active Comparator group

Description:

Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who 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 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).

Treatment:

Drug: Placebo to omarigliptin

Drug: Placebo to glipizide

Biological: Insulin

Drug: Glipizide