A Study to Assess the Safety and Efficacy of Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (T2DM) and Inadequate Glycemic Control (MK-3102-011)

NCT ID: NCT01717313

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 329 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-05
• Study Completion Date: 2015-06-19

Brief Summary

The purpose of this study is to assess the safety and efficacy of omarigliptin (MK-3102), dosed once-weekly in participants with T2DM who have inadequate glycemic control on diet and exercise. The primary hypothesis is that after 24 weeks, treatment with omarigliptin compared with placebo provides greater reduction in hemoglobin A1c (A1C).

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Omarigliptin

Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally once a week plus placebo to metformin daily (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B.

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 25 mg capsule administered orally once a week.

Metformin

Intervention Type: DRUG

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Placebo to metformin

Intervention Type: DRUG

During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).

Glimepiride

Intervention Type: DRUG

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Placebo to Omarigliptin

Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B.

Group Type: PLACEBO_COMPARATOR

Placebo to Omarigliptin

Intervention Type: DRUG

Placebo to omarigliptin capsule administered orally once a week

Metformin

Intervention Type: DRUG

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Glimepiride

Intervention Type: DRUG

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Interventions

Omarigliptin

Omarigliptin 25 mg capsule administered orally once a week.

Intervention Type: DRUG

Placebo to Omarigliptin

Placebo to omarigliptin capsule administered orally once a week

Intervention Type: DRUG

Metformin

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Intervention Type: DRUG

Placebo to metformin

During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).

Intervention Type: DRUG

Glimepiride

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Intervention Type: DRUG

Other Intervention Names

Fortamet®; Glucophage®; Glucophage® XR; Glumetza®; Riomet®; Metgluco®; Glycoran®; Armaryl®

Eligibility Criteria

Inclusion Criteria

• Has type 2 diabetes mellitus
• Participants in India must be ≤65 years of age
• Meets one of the following criteria: currently not on an antihyperglycemic agent (AHA) for >= 12 weeks and has an A1C of >=7% and <=10% or on stable AHA monotherapy or low-dose combination therapy for > 12 weeks and has an A1C of >=6.5% and <=9%
• Participant is one of the following: male, female who is not of reproductive potential, female of reproductive potential who agrees to remain abstinent 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: a thiazolidinedione (TZD) within 4 months of study participation, a glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist or dipeptidyl peptidase IV (DPP-4) inhibitor within 6 months of study participation, insulin or sodium-glucose cotransporter inhibitor within 12 weeks of study participation, omarigliptin at any time prior to study participation
• History of hypersensitivity to DPP-4 inhibitor
• History of intolerance, hypersensitivity or any contraindication to metformin and/or glimepiride or other sulfonylurea
• Is on a weight loss program and 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
• 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 ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
• Is currently being treated for hyperthyroidism or is on thyroid hormone 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 study, including 21 days following the last dose of study drug
• 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)
• Has had new or worsening coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder
• Has poorly controlled hypertension
• History of malignancy <=5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer
• Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
• Pregnant or breastfeeding, or is expecting to conceive during the study, including 21 days following the last dose of 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 a phlebotomy within 8 weeks of study participation, or intends to donate blood products during the study or has received, or is anticipated to receive, blood products within 12 weeks of study participation or during the study

• 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

Home P, Shankar RR, Gantz I, Iredale C, O'Neill EA, Jain L, Pong A, Suryawanshi S, Engel SS, Kaufman KD, Lai E. A randomized, double-blind trial evaluating the efficacy and safety of monotherapy with the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in people with type 2 diabetes. Diabetes Res Clin Pract. 2018 Apr;138:253-261. doi: 10.1016/j.diabres.2017.10.018. Epub 2017 Oct 24.

Reference Type: RESULT

PMID: 29079379 (View on PubMed)

Other Identifiers

2012-003626-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3102-011

Identifier Type: -

Identifier Source: org_study_id