A Study of the Safety and Efficacy of Omarigliptin (MK-3102) Compared With Glimepiride in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin (MK-3102-016)

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 with inadequate glycemic control on metformin monotherapy. The primay hypothesis of the study 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 Study to Evaluate the Safety and Efficacy of the Addition of MK-3102 Compared With the Addition of Glimepiride in Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Omarigliptin
* Drug: Placebo to Omarigliptin
* Drug: Glimepiride
* Drug: Glimepiride Placebo
* Drug: Metformin
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Type 2 diabetes mellitus On a stable dose of metformin (≥1500 mg/day) for at least 12 weeks with inadequate glycemic control Females of reproductive potential agree to remain abstinent or use or have their partner use acceptable methods of birth control Exclusion Criteria: History of type 1 diabetes mellitus or a history of ketoacidosis Treated with any antihyperglycemic agents (AHA) therapies other than the protocol-required metformin within the prior 12 weeks of study participation or with omarigliptin at any time prior to signing informed consent On a weight loss program and is not in the maintenance phase or 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 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 will receive omarigliptin, 25 mg once weekly and placebo matching glimepiride once daily for up to 54 weeks. | Drug: Omarigliptin<br> <br> Drug: Glimepiride Placebo<br> <br> Drug: Metformin<br>* Participants will continue on their stable dose (>=1500 mg/day) of open-label metformin throughout the trial.<br>Drug: Insulin Glargine<br>* Insulin glargine can be used for rescue therapy, if glycemic control is not maintained. Insulin therapy should be initiated as per local country insulin glargine label.<br>|
| Active Comparator: Glimepiride<br>Participants will receive glimepiride titrated to a maximum of 6 mg, once daily, and placebo to omarigliptin, once weekly for up to 54 weeks. | Drug: Placebo to Omarigliptin<br> <br> Drug: Glimepiride<br>* Glimepiride (1 mg and/or 2 mg tablets). During the 54-week double-blind treatment period, glimepiride can be up-titrated, as appropriate, to a maximum total daily dose of 6 mg/day. Throughout the trial, down-titration of glimepiride may also occur based upon the participant's glucose measurements and clinical symptoms of hypoglycemia.<br>* Other names: GLIMY;Drug: Metformin<br>* Participants will continue on their stable dose (>=1500 mg/day) of open-label metformin throughout the trial.<br>Drug: Insulin Glargine<br>* Insulin glargine can be used for rescue therapy, if glycemic control is not maintained. Insulin therapy should be initiated as per local country insulin glargine label.<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 at Week 54 | Hemoglobin A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 54 A1C minus the Week 0 A1C. | Baseline and Week 54 | 
| Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. | Up to Week 57 | 
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Excluding Data After Glycemic Rescue |  | Up to Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose at Week 54 | Blood glucose was measured on a fasting basis. FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline). | Baseline and Week 54 | 
| Percentage of Participants Achieving a Hemoglobin A1C of <6.5% at Week 54 | The percentage of participants who achieved A1C values <6.5% (48 mmol/mol) in the FAS Population at Week 54. | Week 54 | 
| Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Excluding Data After Glycemic Rescue | Symptomatic episode of hypoglycemia was an episode with clinical symptoms reported by the investigator as hypoglycemia (concurrent fingerstick glucose not required). | Up to Week 54 | 
| Change From Baseline in Body Weight at Week 54 Excluding Data After Gylcemic Rescue |  | Baseline and Week 54 | 
| Percentage of Participants Achieving a Hemoglobin A1C of <7.0% at Week 54 | The percentage of participants who achieved A1C values <7.0% (53 mmol/mol) in the FAS Population at Week 54. | Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes