Omarigliptin (MK-3102) Clinical Trial - Add-on to Oral Antihyperglycemic Agent Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-3102-015)

A Phase III, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blinded Study and Subsequent Open-label, Extension Study to Assess the Safety and Efficacy of Addition of MK-3102 in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Oral Antihyperglycemic Agent Monotherapy

This study will examine the safety and efficacy of the addition of omarigliptin in Japanese participants with type 2 diabetes mellitus who have inadequate glycemic control on diet/exercise therapy and oral antihyperglycemic agent monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Omarigliptin; Drug: Matching placebo to omarigliptin

Detailed Description

The treatment period is composed of a 24-week double-blind period (Phase A) and a 28-week open-label period (Phase B). During Phase A, participants will received either omarigliptin 25 mg or a matching placebo. During Phase, B all participants will receive omarigliptin 25 mg. All participants will remain on a stable dose and administration of a single oral antihyperglycemic basal medication.

• Study Type: Interventional
• Enrollment (Actual): 585
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has type 2 diabetes mellitus
• Has inadequate glycemic control on diet/exercise therapy and oral antihyperglycemic agent monotherapy

Exclusion Criteria:

• History of type 1 diabetes mellitus or a history of ketoacidosis
• History of any of the following medications: Thiazolidinediones (TZD) (for participants whose basal medication is not TZD) and/or insulin within 12 weeks prior to study participation, omarigliptin anytime

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omarigliptin 25 mg/Sulfonylureas (SUs) (Phase A+B); Omarigliptin 25 mg administered orally once weekly for 52 weeks (24 weeks during Phase A and 28 weeks during Phase B). Participants continued pre-study basal medication of SUs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Experimental: Omarigliptin 25 mg/Glinides (Phase A+B); Omarigliptin 25 mg administered orally once weekly for 52 weeks (24 weeks during Phase A and 28 weeks during Phase B). Participants continued pre-study basal medication of glinides throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Experimental: Omarigliptin 25 mg/biguanides (BGs) (Phase A+B); Omarigliptin 25 mg administered orally once weekly for 52 weeks (24 weeks during Phase A and 28 weeks during Phase B). Participants continued pre-study basal medication of BGs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Experimental: Omarigliptin 25 mg/Thiazolidinediones (TZDs) (Phase A+B); Omarigliptin 25 mg administered orally once weekly for 52 weeks (24 weeks during Phase A and 28 weeks during Phase B). Participants continued pre-study basal medication of TZDs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Experimental: Omarigliptin 25 mg/α-GIs (Phase A+B); Omarigliptin 25 mg administered orally once weekly for 52 weeks (24 weeks during Phase A and 28 weeks during Phase B). Participants continued pre-study basal medication of α-glucosidase (α-GIs) inhibitors throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Placebo Comparator: Placebo/SUs (Phase A) → Omarigliptin 25 mg/SUs (Phase B); Placebo matching omarigliptin administered orally once weekly for 24 weeks during Phase A. Omarigliptin 25 mg is administered once weekly for 28 weeks during Phase B. Participants continued pre-study basal medication of SUs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).; Drug: Matching placebo to omarigliptin; Matching placebo to omarigliptin 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Placebo Comparator: Placebo/Glinides (Phase A) → Omarigliptin 25 mg/Gln. (Phase B); Placebo matching omarigliptin administered orally once weekly for 24 weeks during Phase A. Omarigliptin 25 mg is administered once weekly for 28 weeks during Phase B. Participants continued pre-study basal medication of glinides throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).; Drug: Matching placebo to omarigliptin; Matching placebo to omarigliptin 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Placebo Comparator: Placebo/BGs (Phase A) → Omarigliptin 25 mg/BGs (Phase B); Placebo matching omarigliptin administered orally once weekly for 24 weeks during Phase A. Omarigliptin 25 mg is administered once weekly for 28 weeks during Phase B. Participants continued pre-study basal medication of BGs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).; Drug: Matching placebo to omarigliptin; Matching placebo to omarigliptin 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Placebo Comparator: Placebo/TZDs (Phase A) → Omarigliptin 25 mg/TZDs (Phase B); Placebo matching omarigliptin administered orally once weekly for 24 weeks during Phase A. Omarigliptin 25 mg is administered once weekly for 28 weeks during Phase B. Participants continued pre-study basal medication of TZDs throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).; Drug: Matching placebo to omarigliptin; Matching placebo to omarigliptin 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).
Placebo Comparator: Placebo/α-GIs (Phase A) → Omarigliptin 25 mg/α-GIs (Phase B); Placebo matching omarigliptin administered orally once weekly for 24 weeks during Phase A. Omarigliptin 25 mg is administered once weekly for 28 weeks during Phase B. Participants continued pre-study basal medication of α-GIs inhibitors throughout the duration of the study.	Drug: Omarigliptin; Omarigliptin (MK-3102) 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).; Drug: Matching placebo to omarigliptin; Matching placebo to omarigliptin 25 mg capsule administered orally once weekly. Pre-study basal medications include: SUs (gliclazide, glibenclamide, or glimepiride); Glinides (nateglinide , mitiglinide, or repaglinide); BGs (metformin); TZDs (pioglitazone); and α-GIs (acarbose, voglibose, or miglitol).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During Phase A	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, that occurs during the course of the study.	Up to 24 weeks
Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue During Phase A	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. Glycemic rescue criteria were: fasting plasma glucose (FPG) of >240 mg/dL, 2 times, (Week 4 to Week 24) and after Week 24, FPG >200 mg/dL, 2 times. Glycemic rescue was achieved through up-titration of basal medication (1st rescue) and through the use of metformin or glimepiride (2nd rescue).	Up to 24 weeks
Percentage of Participants Who Experienced at Least One Adverse Event Excluding Data After Glycemic Rescue During the Overall Study	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. Glycemic rescue criteria were: fasting plasma glucose (FPG) of >240 mg/dL, 2 times, (Week 4 to Week 24) and after Week 24, FPG >200 mg/dL, 2 times. Glycemic rescue was achieved through up-titration of basal medication (1st rescue) and through the use of metformin or glimepiride (2nd rescue). These results represent the accrual of events over different treatment intervals: 52 weeks, Omarigliptin (Phase A+B) group, defined as the double-blind period and open-label extension period versus 28 weeks for the placebo switching to Omarigliptin group defined as the open-label extension period only.	Up to 52 weeks
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event During the Overall Study	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. Glycemic rescue criteria were: fasting plasma glucose (FPG) of >240 mg/dL, 2 times, (Week 4 to Week 24) and after Week 24, FPG >200 mg/dL, 2 times. Glycemic rescue was achieved through up-titration of basal medication (1st rescue) and through the use of metformin or glimepiride (2nd rescue). These results represent the accrual of events over different treatment intervals: 52 weeks, Omarigliptin (Phase A+B) group, defined as the double-blind period and open-label extension period versus 28 weeks for the placebo switching to Omarigliptin group defined as the open-label extension period only.	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24	HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 HbA1c minus the Week 0 HbA1c.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Gantz I, Okamoto T, Ito Y, Sato A, Okuyama K, O'Neill EA, Engel SS, Lai E; Omarigliptin Study 015 Group. A Randomized, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Adding Omarigliptin to Antihyperglycemic Therapies in Japanese Patients with Type 2 Diabetes and Inadequate Glycemic Control. Diabetes Ther. 2017 Aug;8(4):793-810. doi: 10.1007/s13300-017-0270-7. Epub 2017 Jun 6.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2012
• Primary Completion (Actual): May 8, 2014
• Study Completion (Actual): May 8, 2014

Study Registration Dates

• First Submitted: September 28, 2012
• First Submitted That Met QC Criteria: September 28, 2012
• First Posted (Estimate): October 2, 2012

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: August 8, 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
• Other Study ID Numbers: 3102-015; 132242 (Registry Identifier: JAPIC-CTI)

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 Snyopsis