A Study to Evaluate the Safety and Efficacy of Omarigliptin (MK-3102) Compared With Glimepiride in Participants With Type 2 Diabetes Mellitus for Whom Metformin is Inappropriate (MK-3102-027)

Study Overview
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Brief Summary
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This trial will assess the safety and efficacy of omarigliptin (MK-3102) compared with the sulfonylurea, glimepiride, in type 2 diabetes mellitus participants who are metformin intolerant or who have a contraindication to the use of metformin. The primary hypothesis is that after 54 weeks, the mean change from baseline in hemoglobin A1c (A1C) in participants treated with omarigliptin is non-inferior compared with that in participants treated with glimepiride.

Official Title
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A Phase III, Multicenter, Double-Blind, Randomized Trial to Evaluate the Safety and Efficacy of MK-3102 Compared With Glimepiride in Subjects With Type 2 Diabetes Mellitus For Whom Metformin is Inappropriate Due to Intolerance or Contraindication

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Omarigliptin
* Drug: Glimepiride
* Drug: Omarigliptin Placebo
* Drug: Glimepiride Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes mellitus Have intolerability to metformin ≥1000 mg/day or have a contraindication to the use of metformin Females of reproductive potential agree to remain abstinent or use or have their partner use 2 acceptable methods of birth control Exclusion Criteria: History of type 1 diabetes mellitus or a history of ketoacidosis or assessed by the investigator as possibly having type 1 diabetes Has been treated with: A thiazolidinedione (TZD) within 4 months of study participation, or A glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist (such as exenatide or liraglutide) within 6 months of study participation, or Insulin within 12 weeks prior to study participation, or Dual antihyperglycemic agent (AHA) therapy within 12 weeks of study participation (4 months if a component of the dual AHA therapy was a TZD) Omarigliptin (MK-3102) at any time prior to study participation On a weight loss program and is not in the maintenance phase; has started 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) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omarigliptin<br>Participants receive an omarigliptin (MK-3102) 25 mg capsule once weekly and glimepiride placebo tablet(s) once daily, for 54 weeks. | Drug: Omarigliptin<br>* Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly<br>Drug: Glimepiride Placebo<br>* Matching placebo to glimepiride tablet administered orally once daily with breakfast or the first main meal<br>|
| Active Comparator: Glimepiride<br>Participants receive glimepiride 1 mg and/or 2 mg tablet(s) (maximum dose 6 mg/day) once daily and an omarigliptin placebo capsule once weekly, for 54 weeks. | Drug: Glimepiride<br>* Glimepiride tablet 1 mg and/or 2 mg (uptitrated to a maximum dose 6 mg/day) administered orally once daily with breakfast or the first main meal<br>* Other names: GLIMY;Drug: Omarigliptin Placebo<br>* Matching placebo to omarigliptin capsule administered orally once weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1C (A1C) at Week 54 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 54 A1C percent minus the Week 0 A1C percent. | Baseline and Week 54 | 
| Percentage of Participants Who Experienced at Least One Adverse Event | An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions. | Up to 57 weeks (including 3 weeks following the last dose of study drug) | 
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions. | Up to 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | This change from baseline reflects the FPG level at Week 54 minus the FPG level at Week 0. | Baseline and Week 54 | 
| Percentage of Participants Achieving an A1C Goal <7.0% or <6.5% After 54 Weeks of Treatment | Percentage of participants achieving glycemic goal (A1C <7% or <6.5%) after 54 weeks of treatment. | 54 weeks | 
| Percentage of Participants Meeting the Composite Endpoint of an A1C Decrease >0.5%, No Symptomatic Hypoglycemia, and No Body Weight Gain After 54 Weeks of Treatment | Percentage of Participants who had an A1C decrease >0.5%, no symptomatic hypoglycemia, and no body weight gain after 54 weeks of treatment | 54 weeks | 
| Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia | An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. Per protocol, an adverse event was defined as symptomatic hypoglycemia if hypoglycemia was an adverse event collected on the AE form AND the symptoms associated with it were collected on the hypoglycemia assessment (HA) form. Due to the early termination of the study, the HA form information was not assessed; therefore, this endpoint cannot be reported. | Up to 54 weeks | 
| Change From Baseline in Body Weight at Week 54 | Body weight was to be measured (in duplicate) using a calibrated digital scale. | Baseline and Week 54 |