Omarigliptin Add-on to Insulin in Japanese Participants With Type 2 Diabetes Mellitus (T2DM, MK-3102-039)

NCT02906709 | Completed Phase 4 Results

• 3 other identifiers: 3102-039MK-3102-039163455
• Study Type: interventional
• Target: 184
• Locations: 0 countries
• Sites: N/A

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 \[Phase A (double-blind period)\].

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A)

  HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 16 to determine the Constrained Longitudinal Data Analysis least squares mean HbA1c change from baseline (i.e., HbA1c at Week 16 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in HbA1c levels.

  Baseline (Day 1) and Week 16

• Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)

  An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.

  Up to Week 16

• Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])

  An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.

  Up to Week 52

• Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A)

  An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.

  Up to Week 16

• 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])

  An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.

  Up to Week 52

Secondary Outcomes (8)

• Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)

  Baseline (Day 1) and Week 16

• 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)

  Week 16

• 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)

  Week 16

• 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)

  Baseline (Day 1) and Week 16

• Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B)

  Baseline (Day 1) and Week 52

Study Arms (2)

Omarigliptin 25 mg

EXPERIMENTAL

Omarigliptin 25 mg once weekly for 52 weeks (Phase A and B)

Drug: Omarigliptin; Biological: Insulin

Placebo→Omarigliptin 25 mg

EXPERIMENTAL

Placebo to Omarigliptin once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B)

Drug: Omarigliptin; Drug: Placebo; Biological: Insulin

Interventions

Omarigliptin DRUG

Omarigliptin, 25 mg orally once weekly

Also known as: MK-3102, MARIZEV®

Omarigliptin 25 mg; Placebo→Omarigliptin 25 mg

Placebo DRUG

Placebo to omarigliptin orally once weekly

Placebo→Omarigliptin 25 mg

Insulin BIOLOGICAL

Insulin will be administered subcutaneously during the trial as monotherapy; dosage and administration following each package insert.

Omarigliptin 25 mg; Placebo→Omarigliptin 25 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have T2DM
• Meet all of following criteria at Week -2 of pre-randomization
• On diet and exercise therapy for 6 weeks or longer, AND
• Have been on a stable dosage and administration of insulin (8 to 40 units/day) for 10 weeks or longer, AND.
• Have not been on any additional anti-hyperglycemic agent (AHAs, except for insulin monotherapy) for 8 weeks or longer, AND
• HbA1c ≥7.5% and ≤10.0%
• 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.

You may not qualify if:

• 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:
• Thiazolidinediones within 12 weeks
• Glucagon-like peptide 1 (GLP-1) receptor agonists within 12 weeks
• 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:

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 33512755 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2016
• First Posted: September 20, 2016
• Study Start: October 17, 2016
• Primary Completion: August 21, 2018
• Study Completion: August 21, 2018
• Last Updated: September 19, 2019
• Results First Posted: September 19, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share