A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)

NCT01703208 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: 3102-0182012-002414-39MK-3102-018
• Study Type: interventional
• Target: 4,202
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (7)

• Number of Participants With MACE-plus (Confirmed Cardiovascular [CV]-Related Death, Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, or Hospitalization Due to Unstable Angina)

  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)

  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)

  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

  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)

  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

  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

  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 Outcomes (16)

• Number of Participants With an Event of CV-Related Death

  Up to 179 weeks

• Number of Participants With an Event Per 100 Person-Years of CV-Related Death

  Up to 179 weeks

• Number of Participants With an Event of First MI (Fatal and Non-fatal)

  Up to 179 weeks

• Number of Participants With an Event Per 100 Person-Years of First MI (Fatal and Non-fatal)

  Up to 179 weeks

• Number of Participants With an Event of Stroke (Fatal and Non-fatal)

  Up to 179 weeks

Other Outcomes (2)

• Number of Participants With an Event of First Hospitalization for Heart Failure (Exploratory)

  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)

  Up to 179 weeks

Study Arms (2)

Omarigliptin

EXPERIMENTAL

Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly

Drug: Omarigliptin

Placebo

PLACEBO COMPARATOR

Matching placebo to omarigliptin capsule or tablet administered orally once weekly

Drug: Placebo

Interventions

Omarigliptin DRUG

Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly

Omarigliptin

Placebo DRUG

Matching placebo to omarigliptin capsule or tablet administered orally once weekly

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Gantz I, Chen M, Suryawanshi S, Ntabadde C, Shah S, O'Neill EA, Engel SS, Kaufman KD, Lai E. A randomized, placebo-controlled study of the cardiovascular safety of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2017 Sep 11;16(1):112. doi: 10.1186/s12933-017-0593-8.

  PMID: 28893244 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

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialDisclosure@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: October 5, 2012
• First Posted: October 10, 2012
• Study Start: October 5, 2012
• Primary Completion: May 13, 2016
• Study Completion: March 22, 2017
• Last Updated: November 6, 2018
• Results First Posted: December 12, 2017

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share