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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Omarigliptin; Drug: Glimepiride Placebo; Drug: Glimepiride; Drug: Omarigliptin Placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. A thiazolidinedione (TZD) within 4 months of study participation, or
  2. A glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist (such as exenatide or liraglutide) within 6 months of study participation, or
  3. Insulin within 12 weeks prior to study participation, or
  4. Dual antihyperglycemic agent (AHA) therapy within 12 weeks of study participation (4 months if a component of the dual AHA therapy was a TZD)
  5. 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

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 receive an omarigliptin (MK-3102) 25 mg capsule once weekly and glimepiride placebo tablet(s) once daily, for 54 weeks.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly; Drug: Glimepiride Placebo; Matching placebo to glimepiride tablet administered orally once daily with breakfast or the first main meal
Active Comparator: Glimepiride; 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; 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; Other Names: AMARYL®; GLIMY; Drug: Omarigliptin Placebo; Matching placebo to omarigliptin capsule administered orally once weekly

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2013
• Primary Completion (Actual): April 3, 2014
• Study Completion (Actual): April 3, 2014

Study Registration Dates

• First Submitted: May 23, 2013
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• 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; Glimepiride
• Other Study ID Numbers: 3102-027; 2013-000301-23 (EudraCT 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

Study Data/Documents

1. CSR Synopsis Link