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)

August 9, 2018 updated by: Merck Sharp & Dohme LLC

A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of MK-3102 to Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Participants received blinded omarigliptin or matching placebo to omarigliptin for 104 weeks. During the first 24 weeks (Phase A) they did not receive any other blinded study medication. In Phase B (subsequent 80 weeks), participants who did not initiate glycemic rescue in Phase A received additional blinded study medication: participants in the omarigliptin group received placebo to glimepiride and participants in the placebo group received glimepiride.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
402

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

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
  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Omarigliptin (Phase A) → Omarigliptin (Phase B)
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
Omarigliptin 25 mg capsule administered orally once weekly (preferably on the same day of each week)
Other Names:
  • MK-3102
Drug: Matching placebo to glimepiride
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.
Drug: Insulin glargine
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.
Other Names:
  • Lantus
Drug: Metformin
Participants continue stable pre-study dose of metformin tablet(s) administered orally (>= 1500 mg daily) throughout the study.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Placebo Comparator: Placebo to omarigliptin (Phase A) → Glimepiride (Phase B)
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: Insulin glargine
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.
Other Names:
  • Lantus
Drug: Metformin
Participants continue stable pre-study dose of metformin tablet(s) administered orally (>= 1500 mg daily) throughout the study.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Matching placebo to omarigliptin
Matching placebo to omarigliptin capsule administered orally once weekly (preferably on the same day of each week)
Drug: Glimepiride
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.
Other Names:
  • Amaryl®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24 (Phase A)
Time Frame: Baseline and Week 24
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)
Time Frame: Up to 107 weeks
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)
Time Frame: Up to 104 weeks
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)
Time Frame: Up to 104 weeks
The following laboratory parameters were included: blood chemistry, hematology, electrocardiograms, lipids, body weight, and vital signs.
Up to 104 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 (Phase A)
Time Frame: Baseline and Week 24
Change from baseline in 2-hour PMG at Week 24 was analyzed using 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
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A)
Time Frame: Baseline and Week 24
Change from baseline in FPG at Week 24 was analyzed using 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
Change From Baseline in A1C at Week 104 (Phase A+B)
Time Frame: Baseline and Week 104
A1C is measured as a percent. Change from baseline in A1C at Week 104 was analyzed using 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 104
Change From Baseline in FPG at Week 104 (Phase A+B)
Time Frame: Baseline and Week 104
Change from baseline in FPG at Week 104 was analyzed using 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 104
Percentage of Participants Attaining A1C Glycemic Goals of <7.0% After 24 Weeks of Treatment (Phase A)
Time Frame: 24 weeks
Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.
24 weeks
Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 24 Weeks of Treatment (Phase A)
Time Frame: 24 weeks
Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 24 weeks of treatment estimated using standard multiple imputation techniques.
24 weeks
Percentage of Participants Attaining A1C Glycemic Goals of <7% After 104 Weeks of Treatment (Phase A+B)
Time Frame: 104 weeks
Percentage of participants attaining A1C glycemic goals of <7.0% (53 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.
104 weeks
Percentage of Participants Attaining A1C Glycemic Goals of <6.5% After 104 Weeks of Treatment (Phase A+B)
Time Frame: 104 weeks
Percentage of participants attaining A1C glycemic goals of <6.5% (48 mmol/mol) after 104 weeks of treatment estimated using standard multiple imputation techniques.
104 weeks
Change From Baseline in PMG Total Area Under the Plasma Concentration Time Curve (AUC) at Week 24 (Phase A)
Time Frame: Baseline and Week 24
Change from baseline in PMG total AUC at Week 24 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment. Plasma glucose levels were measured before the meal (0 minutes), and at 60 and 120 minutes after the meal.
Baseline and Week 24
Change From Baseline in Fasting Insulin at Week 24 (Phase A)
Time Frame: Baseline and Week 24
Change from baseline in fasting insulin at Week 24 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment.
Baseline and Week 24
Change From Baseline in Fasting Insulin at Week 104 (Phase A+B)
Time Frame: Baseline and Week 104
Change from baseline in fasting insulin at Week 104 based on a cLDA model including terms for treatment, time, and the interaction of time by treatment.
Baseline and Week 104
Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 24 Weeks (Phase A)
Time Frame: Up to 24 weeks
Participants who did not meet progressively stricter glycemic criteria in Phase A had rescue initiated with open-label glimepiride.
Up to 24 weeks
Kaplan-Meier Estimate of Cumulative Incidence of Participants Requiring Glycemic Rescue Therapy by 104 Weeks (Phase A+B)
Time Frame: Up to 104 weeks
Participants who did not meet progressively stricter glycemic criteria in Phase A had rescue initiated with open-label glimepiride. If during Phase B participants on open-label glimepiride or blinded glimepiride/glimepiride matching placebo needed rescue after maximum up-titration, then insulin glargine was initiated and the dose of open-label glimepiride or blinded glimepiride/glimepiride-matching placebo was discontinued.
Up to 104 weeks
Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 24 (Phase A)
Time Frame: Up to 24 weeks
Data presented are a cumulative incidence of participants with glycemic rescue by Week 24.
Up to 24 weeks
Percentage of Participants Requiring Glycemic Rescue Therapy at or Before Week 104 (Phase A+B)
Time Frame: Up to 104 weeks
Data presented are a cumulative incidence of participants with glycemic rescue by Week 104.
Up to 104 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 11, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 16, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 16, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 24, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 3102-024
  • 2012-003670-11 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes Mellitus

Clinical Trials on Omarigliptin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings