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)

NCT01755156 | Completed Phase 3 Results DMC

• 2 other identifiers: 3102-0242012-003670-11
• Study Type: interventional
• Target: 402
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)

  A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using a constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, time, and the interaction of time by treatment.

  Baseline and Week 24

• Percentage of Participants Who Experienced at Least One Adverse Event (Phase A+B)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 107 weeks

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A+B)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 104 weeks

• Percentage of Participants Who Experienced an Adverse Event Which Were Included Under the System Order Class of Investigations (Phase A+B)

  The following laboratory parameters were included: blood chemistry, hematology, electrocardiograms, lipids, body weight, and vital signs.

  Up to 104 weeks

Secondary Outcomes (15)

• Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)

  Baseline and Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A)

  Baseline and Week 24

• Change From Baseline in A1C at Week 104 (Phase A+B)

  Baseline and Week 104

• Change From Baseline in FPG at Week 104 (Phase A+B)

  Baseline and Week 104

• Percentage of Participants Attaining A1C Glycemic Goals of <7.0% After 24 Weeks of Treatment (Phase A)

  24 weeks

Study Arms (2)

Omarigliptin (Phase A) → Omarigliptin (Phase B)

EXPERIMENTAL

Phase A: Omarigliptin 25 mg capsule administered orally once weekly for 24 weeks. Phase B: Omarigliptin 25 mg capsule administered orally once weekly and matching placebo to glimepiride tablet/capsule administered orally once daily for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).

Drug: Omarigliptin; Drug: Matching placebo to glimepiride; Drug: Insulin glargine; Drug: Metformin

Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

PLACEBO COMPARATOR

Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: Matching placebo to omarigliptin capsule administered orally once weekly and glimepiride 1 or 2 mg tablet/capsule administered orally once daily (titrated up to 6 mg daily) for 80 weeks. Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).

Drug: Matching placebo to omarigliptin; Drug: Glimepiride; Drug: Insulin glargine; Drug: Metformin

Interventions

Omarigliptin DRUG

Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week)

Also known as: MK-3102

Omarigliptin (Phase A) → Omarigliptin (Phase B)

Matching placebo to omarigliptin DRUG

Matching placebo to omarigliptin capsule administered orally once weekly (preferably on the same day of each week)

Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

Glimepiride DRUG

Glimepiride 1 or 2 mg tablet/capsule administered orally once daily and up-titrated to a maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Also known as: Amaryl®

Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

Matching placebo to glimepiride DRUG

Matching placebo to glimepiride tablet/capsule administered orally once daily and up-titrated to a mock maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.

Omarigliptin (Phase A) → Omarigliptin (Phase B)

Insulin glargine DRUG

During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.

Also known as: Lantus

Omarigliptin (Phase A) → Omarigliptin (Phase B); Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

Metformin DRUG

Participants continue stable pre-study dose of metformin tablet(s) administered orally (\>= 1500 mg daily) throughout the study.

Also known as: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Omarigliptin (Phase A) → Omarigliptin (Phase B); Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 28547998 RESULT

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; glimepiride; Insulin Glargine; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 24, 2012
• Study Start: January 11, 2013
• Primary Completion: March 16, 2016
• Study Completion: March 16, 2016
• Last Updated: September 10, 2018
• Results First Posted: March 20, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share