Study to Evaluate the Safety and Efficacy of the Addition of Omarigliptin (MK-3102) Compared With the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin (MK-3102-026)

Study Overview
=================
Brief Summary
-----------------
This is a non-inferiority study comparing omarigliptin with sitagliptin in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic control on metformin therapy. The primary hypothesis is that after 24 weeks, the mean change from baseline in hemoglobin A1c (A1C) in participants treated with omarigliptin is non-inferior to that in participants treated with sitagliptin. There will be a 2-week run-in period with placebo + metformin prior to the double-blind treatment period.

Official Title
-----------------
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 Sitagliptin in Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Omarigliptin
* Drug: Sitagliptin
* Drug: Placebo to omarigliptin
* Drug: Placebo to Sitagliptin
* Drug: Open-label Metformin
* Drug: Open-label Glimepiride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes mellitus Currently on a stable dose of metformin monotherapy (≥1500 mg per day) for at least 12 weeks prior to study participation Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain from heterosexual activity or use (or have their partner use) acceptable contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug Exclusion Criteria: History of type 1 diabetes mellitus or a history of ketoacidosis Has been treated with any antihyperglycemic agent (AHA) other than the protocol-required metformin within 12 weeks prior to study participation or with omarigliptin at any time prior to signing informed consent History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor Is currently participating in, or has participated in, a trial in which the participant received an investigational compound or used an investigational device within the prior 12 weeks of signing the informed consent or is not willing to refrain from participating in any other trial History of intolerance, hypersensitivity, or any other contraindication to metformin or sitagliptin Is 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 Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study Is on or likely to require treatment ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) Currently being treated for hyperthyroidism or is on thyroid hormone replacement therapy and has not been on a stable dose for at least 6 weeks Is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days after the last dose of trial medication History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gall bladder disease Human immunodeficiency virus (HIV) New or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or transient ischemic attacks in the past 3 months Poorly controlled hypertension 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 Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) Positive urine pregnancy test Pregnant or breastfeeding, or is expecting to conceive during the study including 21 days following the last dose of blinded study drug User of recreational or illicit drugs or has had a recent history of drug abuse Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study participation, or intends to donate blood products within the projected duration of the trial or has received, or is anticipated to receive, blood products within 12 weeks of study participation or within the projected duration of the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omarigliptin 25 mg once weekly<br>Participants receive omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy. | Drug: Omarigliptin<br>* Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks<br>Drug: Placebo to Sitagliptin<br>* Placebo to sitagliptin 100 mg oral tablet once a day for 24 weeks<br>Drug: Open-label Metformin<br>* Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day<br>* Other names: Riomet®;Drug: Open-label Glimepiride<br>* Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy<br>* Other names: Glimy;|
| Active Comparator: Sitagliptin 100 mg once daily<br>Participants receive sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy. | Drug: Sitagliptin<br>* Sitagliptin 100 mg oral tablet once a day for 24 weeks<br>Drug: Placebo to omarigliptin<br>* Placebo to omarigliptin 25 mg oral capsule once a week for 24 weeks<br>Drug: Open-label Metformin<br>* Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day<br>* Other names: Riomet®;Drug: Open-label Glimepiride<br>* Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy<br>* Other names: Glimy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in A1C at Week 24 | A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline. | Baseline and Week 24 | 
| Percentage of Participants Who Experienced at Least One Adverse Event | An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy. | Up to 27 weeks (including 3-week follow-up) | 
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after initiation of glycemic rescue therapy. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FPG at Week 24 | Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG. | Baseline and Week 24 | 
| Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment | Participant whole blood samples were collected at Week 24 to determine the number of participants achieving A1C <7.0% at Week 24. | Week 24 | 
| Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment | Participant whole blood samples were collected at Week 24 to determine the percentage of participants achieving A1C <6.5% at Week 24. | Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Metformin, Hypoglycemic Agents, Physiological Effects of Drugs, Glimepiride, Pharmacologic Actions