- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01703208
A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)
October 10, 2018 updated by: Merck Sharp & Dohme LLC
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess Cardiovascular Outcomes Following Treatment With MK-3102 in Subjects With Type 2 Diabetes Mellitus
The purpose of this study is to evaluate the cardiovascular (CV) safety profile of omarigliptin in participants with type 2 diabetes mellitus (T2DM).
The primary hypothesis is that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo and active comparators across the omarigliptin program with regard to the risk of developing a confirmed event in the primary CV composite endpoint.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
The trial was amended to extend the length of the trial in order to meet FDA requirements for the post-approval assessment of cardiovascular (CV) safety.
The trial now contains 2 time intervals: Period 1 and Period 2. Period 1 refers to the time interval up to this recent protocol amendment and Period 2, the time interval from this protocol amendment until the end of the study.
Participants in Period 1 will be re-consented and continue into Period 2. If required, additional participants will be enrolled in Period 2. Stage 1 refers to the prefiling United States Food and Drug Administration (US FDA) requirement to rule out a 80% increased CV risk.
Stage 2 refers to the US FDA post-marketing requirement to rule out a 30% increased CV risk.
The Stage 1 assessment of CV risk occurred during Period 1 and was based on a meta-analysis of major adverse CV events (MACE) and unstable angina across the omarigliptin Phase 2/Phase 3 program.
The Stage 2 assessment will be based on MACE in P018 alone including CV events from both Period 1 and Period 2.
Study Type
Interventional
Enrollment (Actual)
4202
Phase
- 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
Ages Eligible for Study
40 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosed with type 2 diabetes mellitus
Is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen:
- A1C >= 6.5% and <= 10.0% (>=48 mmol/mol and <=86 mmol/mol) on: (a) diet or exercise alone (not on antihyperglycemic agent [AHA] for >= 12 weeks) OR (b) monotherapy with metformin (MF), pioglitazone (PIO) or an alpha-glucosidase inhibitor (AGI) or a sodium-glucose cotransporter inhibitor (SGLT2i) OR (c) dual combination therapy with MF, PIO, AGI or SGLT2i OR
- A1C >= 7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on (a) monotherapy with a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i OR
- A1C >=7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on one of the following insulin regimens (with or without metformin): (a) basal insulin (e.g.; insulin glargine, insulin detemir, NPH insulin, degludec) OR (b) prandial insulin (e.g. regular, aspart, lispro, glulisine) OR (c) basal/prandial insulin regimen consisting of multiple dose insulin injections of basal and prandial insulin or the use of pre-mixed insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin 70/30®
- Pre-existing vascular disease (coronary artery disease, ischemic cerebrovascular disease, atherosclerotic peripheral artery disease)
- (1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of 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
- Treated with rosiglitazone, a dipeptidyl peptidase-IV (DPP-4) inhibitor, or a glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to study participation or previously treated with omarigliptin
- 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
- Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
- Human immunodeficiency virus (HIV) as assessed by medical history
- New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke, or transient ischemic neurological disorder within the past 3 months
- 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
- Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
- Pregnant or breast feeding, or is expecting to conceive or donate eggs during the trial, including 21 days following the last dose of study drug
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 |
Intervention / Treatment |
---|---|
Experimental: Omarigliptin
Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly
|
Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly
|
Placebo Comparator: Placebo
Matching placebo to omarigliptin capsule or tablet administered orally once weekly
|
Matching placebo to omarigliptin capsule or tablet administered orally once weekly
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina)
Time Frame: Up to 156 weeks
|
Participants with confirmed MACE-plus events (confirmed cardiovascular, CV-related death, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization due to unstable angina).
In the MK-3102-018 study, MACE plus events had a data cut-off date of April 15, 2015.
|
Up to 156 weeks
|
Number of Participants With an Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Time Frame: Up to 179 weeks
|
Participants with an Event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke).
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-Years for First Event of MACE (Confirmed CV-Related Death, Fatal and Nonfatal MI, and Fatal and Nonfatal Stroke)
Time Frame: Up to 179 weeks
|
Participants with an event of MACE (confirmed cardiovascular, CV-related death, fatal and nonfatal myocardial infarction [MI], and fatal and nonfatal stroke).
Person-years were calculated as the sum of all participants' follow-up time to first event.
|
Up to 179 weeks
|
Change From Baseline in Hemoglobin A1C (A1C) at Week 18
Time Frame: Baseline and Week 18
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
|
Baseline and Week 18
|
Change From Baseline in A1C at Week 18 in a Sub-Study of Participants Taking Insulin (With or Without Metformin)
Time Frame: Baseline and Week 18
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
This change from baseline reflects the Week 18 A1C minus the Week 0 A1C.
|
Baseline and Week 18
|
Percentage of Participants Who Experienced at Least One Adverse Event in a Sub-study of Participants Taking Insulin Excluding Data After Background Antihyperglycemic Agent (AHA) Change
Time Frame: Up to Week 18
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to Week 18
|
Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event in a Sub-Study of Participants Taking Insulin Excluding Data After Background AHA Change
Time Frame: Up to Week 18
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to Week 18
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With an Event of CV-Related Death
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs of cardiovascular-related death.
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-Years of CV-Related Death
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs of cardiovascular-related death.
Person-years were calculated as the sum of all participants' follow-up time to event.
|
Up to 179 weeks
|
Number of Participants With an Event of First MI (Fatal and Non-fatal)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs of fatal and non-fatal MI.
Person-years were calculated as the sum of all participants' follow-up time to first event.
|
Up to 179 weeks
|
Number of Participants With an Event of Stroke (Fatal and Non-fatal)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-Years of First Stroke (Fatal and Non-fatal)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed AEs fatal and non-fatal stroke.
Person-years were calculated as the sum of all participants' follow-up time to event.
|
Up to 179 weeks
|
Number of Participants With an Event of All-Cause Death
Time Frame: Up to 179 weeks
|
All-cause death was death from any cause.
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-Years of the Event of All-Cause Death
Time Frame: Up to 179 weeks
|
All-cause death was death for any cause.
Person-years were calculated as the sum of all participants' follow-up time to event.
|
Up to 179 weeks
|
Change From Baseline in A1C at Week 142
Time Frame: Baseline and Week 142
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
This change from baseline reflects the Week 142 A1C minus the Week 0 A1C.
|
Baseline and Week 142
|
Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at 4 Months
Time Frame: 4 months
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
|
4 months
|
Change From Baseline in Fasting Plasma Glucose (FPG) at 4 Months
Time Frame: Baseline and 4 months
|
This change from baseline reflects the Month 4 FPG minus the Week 0 FPG.
|
Baseline and 4 months
|
Time to Initiation of Long-Term Insulin Therapy in Participants Not Receiving Insulin at Baseline
Time Frame: Up to 179 weeks
|
Long-term insulin therapy was defined as a continuous period of insulin use of more than 3 months.
|
Up to 179 weeks
|
Percentage of Participants Who Experienced at Least One Adverse Event
Time Frame: Up to 234 weeks
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to 234 weeks
|
Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event
Time Frame: Up to 212 weeks
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to 212 weeks
|
Change From Baseline in FPG at Week 18 in a Sub-Study of Participants Taking Insulin
Time Frame: Baseline and Week 18
|
This change from baseline reflects the Week 18 FPG minus the Week 0 FPG.
|
Baseline and Week 18
|
Percentage of Participants Achieving a Target A1C <7.0 % (53 mmol/Mol) at Week 18 in a Sub-Study of Participants Taking Insulin
Time Frame: 18 weeks
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).
Analysis was performed with multiple data imputation.
|
18 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed events of first hospitalization for heart failure.
|
Up to 179 weeks
|
Number of Participants With an Event Per 100 Person-years of the Event of the First Hospitalization for Heart Failure (Exploratory)
Time Frame: Up to 179 weeks
|
Participants with adjudicated and confirmed events of first hospitalization for heart failure.
Person-years were calculated as the sum of all participants' follow-up time to event.
|
Up to 179 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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)
October 5, 2012
Primary Completion (Actual)
May 13, 2016
Study Completion (Actual)
March 22, 2017
Study Registration Dates
First Submitted
October 5, 2012
First Submitted That Met QC Criteria
October 5, 2012
First Posted (Estimate)
October 10, 2012
Study Record Updates
Last Update Posted (Actual)
November 6, 2018
Last Update Submitted That Met QC Criteria
October 10, 2018
Last Verified
October 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3102-018
- 2012-002414-39 (EudraCT Number)
- MK-3102-018 (Other Identifier: Merck study 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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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.
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