Study to Evaluate the Safety and Efficacy of the Addition of Omarigliptin (MK-3102) Compared With the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin (MK-3102-026)

NCT01841697 | Completed Phase 3 Results DMC

• 2 other identifiers: 3102-0262013-000059-42
• Study Type: interventional
• Target: 642
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a non-inferiority study comparing omarigliptin with sitagliptin in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic control on metformin therapy. The primary hypothesis is that after 24 weeks, the mean change from baseline in hemoglobin A1c (A1C) in participants treated with omarigliptin is non-inferior to that in participants treated with sitagliptin. There will be a 2-week run-in period with placebo + metformin prior to the double-blind treatment period.

Conditions

Type 2 Diabetes

Keywords

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Glimepiride; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in A1C at Week 24

  A1C is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the least squares mean A1C change from baseline.

  Baseline and Week 24

• Percentage of Participants Who Experienced at Least One Adverse Event

  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. Data presented below excludes data after initiation of glycemic rescue therapy.

  Up to 27 weeks (including 3-week follow-up)

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

  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. Data presented below excludes data after initiation of glycemic rescue therapy.

  Up to 24 weeks

Secondary Outcomes (3)

• Change From Baseline in FPG at Week 24

  Baseline and Week 24

• Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment

  Week 24

• Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment

  Week 24

Study Arms (2)

Omarigliptin 25 mg once weekly

EXPERIMENTAL

Participants receive omarigliptin 25 mg once a week plus placebo to sitagliptin once daily for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Drug: Omarigliptin; Drug: Placebo to Sitagliptin; Drug: Open-label Metformin; Drug: Open-label Glimepiride

Sitagliptin 100 mg once daily

ACTIVE COMPARATOR

Participants receive sitagliptin 100 mg once daily plus placebo to omarigliptin once a week for 24 weeks. Participants continue pre-study stable dose of metformin (total daily dose ≥1500 mg) throughout the study. Participants may receive glimepiride (total daily dose of 1-6 mg) as rescue therapy.

Drug: Sitagliptin; Drug: Placebo to omarigliptin; Drug: Open-label Metformin; Drug: Open-label Glimepiride

Interventions

Omarigliptin DRUG

Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks

Omarigliptin 25 mg once weekly

Sitagliptin DRUG

Sitagliptin 100 mg oral tablet once a day for 24 weeks

Sitagliptin 100 mg once daily

Placebo to omarigliptin DRUG

Placebo to omarigliptin 25 mg oral capsule once a week for 24 weeks

Sitagliptin 100 mg once daily

Placebo to Sitagliptin DRUG

Placebo to sitagliptin 100 mg oral tablet once a day for 24 weeks

Omarigliptin 25 mg once weekly

Open-label Metformin DRUG

Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day

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

Omarigliptin 25 mg once weekly; Sitagliptin 100 mg once daily

Open-label Glimepiride DRUG

Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy

Also known as: Amaryl®, Glimy

Omarigliptin 25 mg once weekly; Sitagliptin 100 mg once daily

Eligibility Criteria

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

You may qualify if:

• 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
• Is currently participating in, or has participated in, a trial in which the participant received an investigational compound or used an investigational device within the prior 12 weeks of signing the informed consent or is not willing to refrain from participating in any other trial
• History of intolerance, hypersensitivity, or any other contraindication to metformin or sitagliptin
• 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 ≥14 consecutive days 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 trial medication
• History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gall bladder 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Goldenberg R, Gantz I, Andryuk PJ, O'Neill EA, Kaufman KD, Lai E, Wang YN, Suryawanshi S, Engel SS. Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes Metab. 2017 Mar;19(3):394-400. doi: 10.1111/dom.12832. Epub 2017 Jan 17.

  PMID: 28093853 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Interventions

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

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2013
• First Posted: April 26, 2013
• Study Start: June 13, 2013
• Primary Completion: November 17, 2014
• Study Completion: November 17, 2014
• Last Updated: September 10, 2018
• Results First Posted: November 25, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share