A Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of Omarigliptin (MK-3102) to Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy (MK-3102-024)

NCT ID: NCT01755156

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-11
• Study Completion Date: 2016-03-16

Brief Summary

The purpose of this study is to assess the safety and efficacy of omarigliptin compared to placebo in participants with inadequate glycemic control on metformin monotherapy. The primary hypothesis is that after 24 weeks, the addition of treatment with omarigliptin provides greater reduction in hemoglobin A1c (A1C) than placebo.

Detailed Description

Participants received blinded omarigliptin or matching placebo to omarigliptin for 104 weeks. During the first 24 weeks (Phase A) they did not receive any other blinded study medication. In Phase B (subsequent 80 weeks), participants who did not initiate glycemic rescue in Phase A received additional blinded study medication: participants in the omarigliptin group received placebo to glimepiride and participants in the placebo group received glimepiride.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Omarigliptin (Phase A) → Omarigliptin (Phase B)

Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week)

Matching placebo to glimepiride

Intervention Type: DRUG

Matching placebo to glimepiride tablet/capsule administered orally once daily and up-titrated to a mock maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Insulin glargine

Intervention Type: DRUG

During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.

Metformin

Intervention Type: DRUG

Participants continue stable pre-study dose of metformin tablet(s) administered orally (\>= 1500 mg daily) throughout the study.

Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).

Group Type: PLACEBO_COMPARATOR

Matching placebo to omarigliptin

Intervention Type: DRUG

Matching placebo to omarigliptin capsule administered orally once weekly (preferably on the same day of each week)

Glimepiride

Intervention Type: DRUG

Glimepiride 1 or 2 mg tablet/capsule administered orally once daily and up-titrated to a maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Insulin glargine

Intervention Type: DRUG

During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.

Metformin

Intervention Type: DRUG

Participants continue stable pre-study dose of metformin tablet(s) administered orally (\>= 1500 mg daily) throughout the study.

Interventions

Omarigliptin

Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week)

Intervention Type: DRUG

Matching placebo to omarigliptin

Matching placebo to omarigliptin capsule administered orally once weekly (preferably on the same day of each week)

Intervention Type: DRUG

Glimepiride

Glimepiride 1 or 2 mg tablet/capsule administered orally once daily and up-titrated to a maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Intervention Type: DRUG

Matching placebo to glimepiride

Matching placebo to glimepiride tablet/capsule administered orally once daily and up-titrated to a mock maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Intervention Type: DRUG

Insulin glargine

During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.

Intervention Type: DRUG

Metformin

Participants continue stable pre-study dose of metformin tablet(s) administered orally (\>= 1500 mg daily) throughout the study.

Intervention Type: DRUG

Other Intervention Names

MK-3102; Amaryl®; Lantus; Fortamet®; Glucophage®; Glucophage® XR; Glumetza®; Riomet®; Metgluco®; Glycoran®

Eligibility Criteria

Inclusion Criteria

• Has 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
• History of intolerance, hypersensitivity, or any other contraindication to metformin, glimepiride, or insulin glargine
• 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 for >=2 consecutive weeks 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 blinded study medication
• History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Shankar RR, Inzucchi SE, Scarabello V, Gantz I, Kaufman KD, Lai E, Ceesay P, Suryawanshi S, Engel SS. A randomized clinical trial evaluating the efficacy and safety of the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Curr Med Res Opin. 2017 Oct;33(10):1853-1860. doi: 10.1080/03007995.2017.1335637. Epub 2017 Jun 23.

Reference Type: RESULT

PMID: 28547998 (View on PubMed)

Other Identifiers

2012-003670-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3102-024

Identifier Type: -

Identifier Source: org_study_id