Clinical trial NCT01698775: 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)
Official title: A Phase III, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of MK-3102 Versus Placebo in Subjects With Type 2 Diabetes Mellitus With Moderate or Severe Chronic Kidney Disease or Kidney Failure on Dialysis Who Have Inadequate Glycemic Control.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-10-03
Enrollment: 213
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period)
timeFrame: Up to 28 weeks (including 28 days following the last dose of study therapy for participants who discontinued study drug)
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)
timeFrame: Up to 24 weeks
measure: Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
timeFrame: Up to 58 weeks (including 28 days following the last dose of study therapy)
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
timeFrame: Up to 54 weeks
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in A1C at Week 54
timeFrame: Baseline and Week 54
measure: Change From Baseline in FPG at Week 54
timeFrame: Baseline and Week 54
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in eGFR at Week 54
timeFrame: Baseline and Week 54
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Chacra A, Gantz I, Mendizabal G, Durlach L, O'Neill EA, Zimmer Z, Suryawanshi S, Engel SS, Lai E. A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment. Int J Clin Pract. 2017 Jun;71(6):e12955. doi: 10.1111/ijcp.12955. Epub 2017 Apr 27.