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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo to metformin; Drug: Omarigliptin; Drug: Metformin; Drug: Placebo to Omarigliptin; Drug: Glimepiride

Study type: Interventional

Funder types: Industry

Identifiers

NCT01717313

3102-011

2012-003626-24 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 329 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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329 participants in 2 patient groups, including a placebo group

Omarigliptin

Experimental group

Description:

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.

Treatment:

Drug: Placebo to metformin

Drug: Omarigliptin

Drug: Glimepiride

Drug: Metformin

Placebo to Omarigliptin

Placebo Comparator group

Description:

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.

Treatment:

Drug: Glimepiride

Drug: Metformin

Drug: Placebo to Omarigliptin