Clinical trial NCT02906709: Omarigliptin Add-on to Insulin in Japanese Participants With Type 2 Diabetes Mellitus (T2DM, MK-3102-039)
Official title: A Phase IV, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial and Subsequent Open-Label, Extension Trial to Assess the Safety and Efficacy of Addition of Omarigliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Monotherapy in Addition to Diet and Exercise Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 184
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the efficacy of omarigliptin 25 mg once weekly compared to placebo in Japanese patients with T2DM who have inadequate glycemic control on insulin monotherapy in addition to diet and exercise therapy. The primary hypothesis of the study is that omarigliptin 25 mg once weekly provides greater reduction in hemoglobin A1C (HbA1c) compared with placebo as assessed by change from baseline to Week 16 \[Phase A (double-blind period)\].

Detailed description: After a screening period of up to 2 weeks followed by a pretreatment period of 2 or 10 weeks, each participant will be receiving assigned double-blind treatment (omarigliptin 25 mg or placebo once weekly) for approximately 16 weeks (Phase A) followed by 36 weeks of open-label treatment (omarigliptin 25 mg once weekly, Phase B). After the end of treatment each participant will be followed for 21 days.

Eligibility criteria: Inclusion Criteria:

* Have T2DM
* Meet all of following criteria at Week -2 of pre-randomization

  1. On diet and exercise therapy for 6 weeks or longer, AND
  2. Have been on a stable dosage and administration of insulin (8 to 40 units/day) for 10 weeks or longer, AND.
  3. Have not been on any additional anti-hyperglycemic agent (AHAs, except for insulin monotherapy) for 8 weeks or longer, AND
  4. HbA1c ≥7.5% and ≤10.0%
  5. Fasting Plasma Glucose (FPG) ≥126 mg/dL and ≤230 mg/dL
* Have a body mass index (BMI) \>18 kg/m\^2 and \<40 kg/m\^2
* A male or female not of reproductive potential or a female of reproductive potential and agrees to remain abstinent from heterosexual activity, or agrees to use acceptable contraception to prevent pregnancy.

Exclusion Criteria:

* Has type 1 diabetes mellitus or has a history of diabetic ketoacidosis.
* Has a history of being administered any of the following AHAs including fixed dose combination (FDC) containing the following ingredients:

  1. Thiazolidinediones within 12 weeks
  2. Glucagon-like peptide 1 (GLP-1) receptor agonists within 12 weeks
  3. Omarigliptin at any time
* Has history of severe hypoglycemia with coma or loss of consciousness, or for whom hypoglycemia was observed greater or equal to two times per week within 8 weeks
* Is currently participating in or has participated in another study with an investigational compound or device within the prior 12 weeks
* Has undergone a surgical procedure within 8 weeks or has planned major surgery during the study.
* Receives a lipid-lowering medication or thyroid replacement therapy at unstable dosage and administration
* Has poorly controlled hypertension
* Has a medical history of active liver disease, including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
* Has human immunodeficiency virus (HIV).
* Has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder within the past 3 months
* Has severe peripheral vascular disease.
* Has a history of malignancy ≤ 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer:
* Has a clinically important hematological disorder.
* (For women of childbearing potential) has a positive urine pregnancy test.
* Is pregnant or breast feeding
* Is expected to conceive during the study
* Is expected to undergo hormonal therapy in preparation to donate eggs during the study
* Routinely consumes \>14 alcoholic drinks per week or engages in binge drinking
* Has donated or plans to donate blood products of \>300 mL within 8 weeks or during the study
* Has received or plans to receive blood products within 12 weeks or during the study

Primary outcomes:
measure: Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Baseline (Day 1) and Week 16
measure: Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Up to Week 16
measure: Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
timeFrame: Up to Week 52
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Up to Week 16
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
timeFrame: Up to Week 52
Secondary outcomes:
measure: Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Baseline (Day 1) and Week 16
measure: Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Week 16
measure: Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Week 16
measure: Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
timeFrame: Baseline (Day 1) and Week 16
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B)
timeFrame: Baseline (Day 1) and Week 52
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B)
timeFrame: Baseline (Day 1) and Week 52
measure: Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B)
timeFrame: Week 52
measure: Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B)
timeFrame: Week 52
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kadowaki T, Seino Y, Kaku K, Okamoto T, Kameya M, Sato A, Hirano T, Oshima N, Gantz I, O'Neill EA, Engel SS; Omarigliptin Study 039 Group. A randomized, placebo-controlled study to evaluate the efficacy and safety of adding omarigliptin to insulin therapy in Japanese patients with type 2 diabetes and inadequate glycaemic control. Diabetes Obes Metab. 2021 Jun;23(6):1242-1251. doi: 10.1111/dom.14331. Epub 2021 Feb 17.