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)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Omarigliptin; Drug: Glimepiride Placebo; Drug: Metformin; Drug: Insulin Glargine; Drug: Placebo to Omarigliptin; Drug: Glimepiride

• Study Type: Interventional
• Enrollment (Actual): 751
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omarigliptin; Participants will receive omarigliptin, 25 mg once weekly and placebo matching glimepiride once daily for up to 54 weeks.	Drug: Omarigliptin; Drug: Glimepiride Placebo; Drug: Metformin; Participants will continue on their stable dose (>=1500 mg/day) of open-label metformin throughout the trial.; Drug: Insulin Glargine; 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.
Active Comparator: Glimepiride; 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: Metformin; Participants will continue on their stable dose (>=1500 mg/day) of open-label metformin throughout the trial.; Drug: Insulin Glargine; 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.; Drug: Placebo to Omarigliptin; Drug: Glimepiride; 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.; Other Names: AMARYL®; GLIMY

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Handelsman Y, Lauring B, Gantz I, Iredale C, O'Neill EA, Wei Z, Suryawanshi S, Kaufman KD, Engel SS, Lai E. A randomized, double-blind, non-inferiority trial evaluating the efficacy and safety of omarigliptin, a once-weekly DPP-4 inhibitor, or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Curr Med Res Opin. 2017 Oct;33(10):1861-1868. doi: 10.1080/03007995.2017.1335638. Epub 2017 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2012
• Primary Completion (Actual): January 26, 2015
• Study Completion (Actual): January 26, 2015

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (Estimate): September 11, 2012

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Metformin; Insulin Glargine; Glimepiride
• Other Study ID Numbers: 3102-016; MK-3102-016 (Other Identifier: protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf