Clinical trial NCT01717313: 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)
Official title: A Multicenter, Phase III, Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of MK-3102 Monotherapy in Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-10-30
Enrollment: 329
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 (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).


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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (A1C) at Week 24 (Phase A, FAS Population)
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Experienced at Least One Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population)
timeFrame: Up to 27 weeks
measure: Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population)
timeFrame: Up to 24 weeks
measure: Percentage of Participants Who Experienced at Least One Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population)
timeFrame: Up to 57 weeks
measure: Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population)
timeFrame: Up to 57 weeks
Secondary outcomes:
measure: Percentage of Participants Who Achieve an A1C Goal of <7% (53 mmol/Mol) at Week 24 (Phase A, FAS Population)
timeFrame: Week 24
measure: Percentage of Participants Who Achieve an A1C Goal of <6.5% (48 mmol/Mol) at Week 24 (Phase A, FAS Population)
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A, FAS Population)
timeFrame: Baseline and Week 24
measure: Change From Baseline in 2-hour Post Meal Glucose (PMG) at Week 24 (Phase A, FAS Population)
timeFrame: Baseline and Week 24
measure: Change From Baseline in A1C at Week 54 (Phase A + Phase B, FAS Population)
timeFrame: Baseline and Week 54
measure: Percentage of Participants Who Achieve an A1C Goal of <7% (53 mmol/Mol) at Week 54 (Phase A + Phase B, FAS Population)
timeFrame: Week 54
measure: Percentage of Participants Who Achieve an A1C Goal of <6.5% at Week 54 (Phase A + Phase B, FAS Population)
timeFrame: Week 54
measure: Change From Baseline in FPG at Week 54 (Phase A + Phase B, FAS Population)
timeFrame: Baseline and Week 54
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.