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) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: Omarigliptin Drug: Sitagliptin Drug: Placebo to omarigliptin Drug: Placebo to Sitagliptin Drug: Open-label Metformin Drug: Open-label Glimepiride	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III, Multicenter, Double-Blind, Randomized Study to Evaluate the Safety and Efficacy of the Addition of MK-3102 Compared With the Addition of Sitagliptin in Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin

Resource links provided by NLM:

Drug Information available for: Metformin Metformin hydrochloride Glimepiride Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Change From Baseline in A1C at Week 24 [ Time Frame: Baseline and 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.
Percentage of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to 27 weeks (including 3-week follow-up) ]
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.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ]
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.

Secondary Outcome Measures:

Change From Baseline in FPG at Week 24 [ Time Frame: Baseline and Week 24 ]
Participant whole blood samples were collected after an overnight fast at baseline and Week 24 to determine the least squares mean change from baseline in participant FPG.
Percentage of Participants Achieving an A1C Goal <7.0% After 24 Weeks of Treatment [ Time Frame: Week 24 ]
Participant whole blood samples were collected at Week 24 to determine the number of participants achieving A1C <7.0% at Week 24.
Percentage of Participants Achieving an A1C Goal <6.5% After 24 Weeks of Treatment [ Time Frame: Week 24 ]
Participant whole blood samples were collected at Week 24 to determine the percentage of participants achieving A1C <6.5% at Week 24.


Enrollment:	642
Actual Study Start Date:	June 13, 2013
Study Completion Date:	November 17, 2014
Primary Completion Date:	November 17, 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Omarigliptin 25 mg once weekly 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 Omarigliptin (MK-3102) 25 mg oral capsule once a week for 24 weeks Drug: Placebo to Sitagliptin Placebo to sitagliptin 100 mg oral tablet once a day for 24 weeks Drug: Open-label Metformin Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day Other Names: Fortamet® Glucophage® Glucophage® XR Glumetza® Riomet® Drug: Open-label Glimepiride Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy Other Names: Amaryl® Glimy
Active Comparator: Sitagliptin 100 mg once daily 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 Sitagliptin 100 mg oral tablet once a day for 24 weeks Drug: Placebo to omarigliptin Placebo to omarigliptin 25 mg oral capsule once a week for 24 weeks Drug: Open-label Metformin Metformin oral tablet(s) - total daily dose of ≥1500 mg, once or twice a day Other Names: Fortamet® Glucophage® Glucophage® XR Glumetza® Riomet® Drug: Open-label Glimepiride Glimepiride oral tablet(s) - total daily dose of 1 to 6 mg once a day as rescue therapy Other Names: Amaryl® Glimy

Arms

Assigned Interventions

Experimental: Omarigliptin 25 mg once weekly

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

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

Drug: Placebo to Sitagliptin

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

Drug: Open-label Metformin

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

Other Names:

Fortamet®
Glucophage®
Glucophage® XR
Glumetza®
Riomet®

Drug: Open-label Glimepiride

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

Other Names:

Amaryl®
Glimy

Active Comparator: Sitagliptin 100 mg once daily

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

Sitagliptin 100 mg oral tablet once a day for 24 weeks

Drug: Placebo to omarigliptin

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

Drug: Open-label Metformin

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

Other Names:

Fortamet®
Glucophage®
Glucophage® XR
Glumetza®
Riomet®

Drug: Open-label Glimepiride

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

Other Names:

Amaryl®
Glimy

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
Positive urine pregnancy test
Pregnant or breastfeeding, or is expecting to conceive during the study including 21 days following the last dose of blinded 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 phlebotomy of >300 mL within 8 weeks of study participation, or intends to donate blood products within the projected duration of the trial or has received, or is anticipated to receive, blood products within 12 weeks of study participation or within the projected duration of the trial

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01841697

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Director	Merck Sharp & Dohme Corp.

More Information

Publications:

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.

Study Data/Documents: CSR Synopsis This link exits the ClinicalTrials.gov site


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT01841697 History of Changes
Other Study ID Numbers:	3102-026 2013-000059-42 ( EudraCT Number )
First Submitted:	April 24, 2013
First Posted:	April 26, 2013
Results First Submitted:	October 23, 2015
Results First Posted:	November 25, 2015
Last Update Posted:	June 29, 2017
Last Verified:	June 2017

Keywords provided by Merck Sharp & Dohme Corp.:


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

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Glimepiride Metformin Sitagliptin Phosphate Hypoglycemic Agents Physiological Effects of Drugs	Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Arrhythmia Agents Immunosuppressive Agents Immunologic Factors