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

This study has been terminated.
(The study was terminated for business reasons and not due to any safety or efficacy concerns related to omarigliptin.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01703208
First received: October 5, 2012
Last updated: May 19, 2016
Last verified: May 2016
History of Changes

October 5, 2012
May 19, 2016
October 2012
May 2016   (final data collection date for primary outcome measure)
  • Time to first event in the cardiovascular (CV) composite endpoint of CV-related death, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina requiring hospitalization (Stage 1) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in hemoglobin A1C (A1C) at Week 18 in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Percentage of participants who experienced at least one adverse event in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Up to Week 18 ] [ Designated as safety issue: Yes ]
  • Percentage of participants who discontinued from study drug due to an adverse event in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Up to Week 18 ] [ Designated as safety issue: Yes ]
  • Time to first event in the cardiovascular (CV) composite endpoint of CV-related death, nonfatal myocardial infarction (MI), or nonfatal stroke (Stage 2) [ Time Frame: Up to 8 years (from the first randomization date, 2012-Dec) ] [ Designated as safety issue: Yes ]
  • Change from baseline in A1C at 4 months [ Time Frame: Baseline and 4 months ] [ Designated as safety issue: No ]
Time to first event in primary cardiovascular (CV) composite endpoint (CV-related death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina requiring hospitalization) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01703208 on ClinicalTrials.gov Archive Site
  • Time to first composite CV endpoint of confirmed CV-related death, nonfatal MI, and nonfatal stroke (Stage 1) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to first event for each of the individual CV endpoints: confirmed CV-related death, MI (fatal + nonfatal), stroke (fatal + nonfatal), and unstable angina requiring hospitalization (Stage 1) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to all-cause mortality (Stage 1) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in A1C at Week 156 [ Time Frame: Baseline and Week 156 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) at 4 months [ Time Frame: Baseline and 4 months ] [ Designated as safety issue: No ]
  • Percentage of participants achieving a target A1C <7.0 % (53 mmol/mol) at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Time to initiation of long-term insulin therapy (long-term insulin therapy is defined as a continuous period of insulin use of more than 3 months) in participants not receiving insulin at baseline [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Change from baseline in FPG at Week 18 in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Percentage of participants achieving a target A1C <7.0 % (53 mmol/mol) at Week 18 in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Percentage of participants who experienced at least one adverse event [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Percentage of participants who discontinued from study drug due to an adverse event [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Time to first event for each of the individual CV endpoints: confirmed CV-related death, MI (fatal + nonfatal), and stroke (fatal + nonfatal) (Stage 2) [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Time to all-cause mortality (Stage 2) [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Time to first major adverse cardiac event (CV-related death, nonfatal myocardial infarction, and nonfatal stroke) [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to CV-related death [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to nonfatal myocardial infarction [ Time Frame: up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to nonfatal stroke [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]
  • Time to unstable angina requiring hospitalization [ Time Frame: up to 156 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study to Assess Cardiovascular Outcomes Following Treatment With Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (MK-3102-018)
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.
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.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Omarigliptin
  • Drug: Placebo
  • Experimental: Omarigliptin
    Omarigliptin (MK-3102) 25 mg capsule or tablet administered orally once weekly
    Intervention: Drug: Omarigliptin
  • Placebo Comparator: Placebo
    Matching placebo to omarigliptin capsule or tablet administered orally once weekly
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4202
May 2016
May 2016   (final data collection date for primary outcome measure)

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:

    1. 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
    2. 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
    3. 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
Both
40 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Colombia,   Croatia,   Czech Republic,   Denmark,   Finland,   France,   Georgia,   Germany,   Hong Kong,   Hungary,   Israel,   Italy,   Korea, Republic of,   Lebanon,   Lithuania,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Philippines,   Poland,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Ukraine,   United Kingdom,   United States
 
NCT01703208
3102-018, 2012-002414-39
Yes
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP