Clinical trial NCT01755156: 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)
Official title: A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of MK-3102 to Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-12-24
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Experienced at Least One Adverse Event (Phase A+B)
timeFrame: Up to 107 weeks
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A+B)
timeFrame: Up to 104 weeks
measure: Percentage of Participants Who Experienced an Adverse Event Which Were Included Under the System Order Class of Investigations (Phase A+B)
timeFrame: Up to 104 weeks
Secondary outcomes:
measure: Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A)
timeFrame: Baseline and Week 24
measure: Change From Baseline in A1C at Week 104 (Phase A+B)
timeFrame: Baseline and Week 104
measure: Change From Baseline in FPG at Week 104 (Phase A+B)
timeFrame: Baseline and Week 104
measure: Percentage of Participants Attaining A1C Glycemic Goals of <7.0% After 24 Weeks of Treatment (Phase A)
timeFrame: 24 weeks
measure: Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 24 Weeks of Treatment (Phase A)
timeFrame: 24 weeks
measure: Percentage of Participants Attaining A1C Glycemic Goals of <7% After 104 Weeks of Treatment (Phase A+B)
timeFrame: 104 weeks
measure: Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 104 Weeks of Treatment (Phase A+B)
timeFrame: 104 weeks
measure: Change From Baseline in PMG Total Area Under the Plasma Concentration Time Curve (AUC) at Week 24 (Phase A)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Fasting Insulin at Week 24 (Phase A)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Fasting Insulin at Week 104 (Phase A+B)
timeFrame: Baseline and Week 104
measure: Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 24 Weeks (Phase A)
timeFrame: Up to 24 weeks
measure: Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 104 Weeks (Phase A+B)
timeFrame: Up to 104 weeks
measure: Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 24 (Phase A)
timeFrame: Up to 24 weeks
measure: Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 104 (Phase A+B)
timeFrame: Up to 104 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.