A Phase 3 study in Patients with Type 2 Diabetes Mellitus

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2012-002414-39-FI
• Date of registration: 20/11/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: A Phase 3 study in Patients with Type 2 Diabetes Mellitus
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess Cardiovascular Outcomes Following Treatment with MK-3102 in Subjects with Type 2 Diabetes Mellitus
• Date of first enrolment: 12/08/2013
• Target sample size: 4000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002414-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Finland, France, Georgia, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Having T2DM and is =40 years of age.
2. Subject 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:
- An A1C =6.5 and =10.0% (=48 mmol/mol and =86 mmol/mol) on
diet and exercise alone (not on an AHA for =12 weeks)
OR
monotherapy with metformin (MF); pioglitazone (PIO); an alpha-glucosidase inhibitor (AGI); or an SGLT2 inhibitor (SGLT2i)
OR
dual combination therapy with MF, PIO, AGI or SGLT2i
OR
- An A1C =7.0% and =10.0% (=53 mmol/mol and =86 mmol/mol) on
monotherapy with a sulfonylurea or meglitinide
OR
dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i
OR
- An A1C =7.0% and =10.0% (=53 mmol/mol and =86 mmol/mol) on one of the following insulin regimens (with or without metformin)
basal insulin (e.g., insulin glargine, insulin detemir, NPH insulin, degludec)
prandial insulin (e.g., regular, aspart, lispro, glulisine)
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®)
Note: A stable insulin regimen is defined as no change in the insulin regimen (i.e. type[s] of insulin) and =10% change in the total daily dose of insulin. For example, if the total daily dose of insulin is 50 U/day, doses of 45-55 U/day would be considered as stable.
3. Having following preexisting vascular disease:
(a) History of a major clinical manifestation of coronary artery disease (i.e., myocardial infarction, surgical or percutaneous [balloon and/or stent] coronary revascularization procedure, or coronary angiography showing at least one stenosis =50% in a major epicardial artery or branch vessel);
(b)Ischemic cerebrovascular disease, including:
- History of ischemic stroke
- History of carotid arterial disease as documented by =50% stenosis documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography, with or without symptoms of neurologic deficit.
(c) Atherosclerotic peripheral arterial disease, as documented by objective - amputation due to vascular disease, current symptoms of intermittent claudication confirmed by an ankle-brachial pressure index of less than 0.9 or a toe-brachial pressure index less than 0.7 or history of surgical or percutaneous revascularization procedure.
4.Meets one of the following criteria:
a. Subject is a male
b. Subject is a female not of reproductive potential defined as one who has either:
(1) reached natural menopause (defined as =12 months of spontaneous amenorrhea in women >45 years of age, or =6 months of spontaneous amenorrhea with serum follicular stimulating hormone [FSH] levels in the postmenopausal range as determined by the laboratory), or
(2)had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least
Exclusion criteria:
1. History of type 1 diabetes mellitus or a history of ketoacidosis or possibly having type 1 diabetes
2. Beeing treated with rosiglitazone, a DPP-4 inhibitor or a GLP-1 receptor agonist within the prior 12 weeks of Visit 1/Screening or previously treated with MK-3102.
3. Having a history of hypersensitivity to a DPP-4 inhibitor
4. Participation in trial with investigational compound prior 12 weeks of signing the informed consent or is not willing to refrain from participating in another trial.
5. Subject is on a weight loss program and is not in the maintenance phase; has been on a weight loss medication in the past 6 months; or has undergone bariatric surgery within 12 months prior to signing the informed consent.
6. Surgical procedure within 4 weeks prior to signing informed consent or has planned major surgery during the trial.
7. Treatment for =14 consecutive days or repeated courses of pharmacologic doses of corticosteroids
8. Treatement for hyperthyroidism or thyroid replacement therapy and has not been on a stable dose for at least 6 weeks.
9. Medical history of active liver disease
10. Human immunodeficiency virus (HIV) as assessed by medical history.
11. Worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months.
12. Poorly-controlled hypertension
13. History of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
14. Clinically important hematological disorder
15. Exclusionary laboratory values
16. Positive urine pregnancy test.
17.Subject is pregnant or breast-feeding, or is expecting to conceive during the trial, including 21 days following the last dose of blinded study medication. OR is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days following the last dose of blinded study medication.
18. Subject is,at the time of signing informed consent,a user of recreational or illicit drugs or has had a recent history of drug abuse.
19. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per
week, or engages in binge drinking.
20. History or current evidence of condition, therapy, lab abnormality or other circumstance that
•makes participation not in the subject’s best interest
•might interfere with subject´s participation for the full duration of the trial, or
•might confound the result of the trial.
21.Subject has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent, or intends to donate blood products within the projected duration of the trial OR received, or anticipated to receive blood products within 12 weeks of signing informed consent or within the projected duration of the trial.
22. Subject is unlikely to adhere to the trial procedures, keep appointments.
23.Symptomatic hyperglycemia that, in the investigator's opinion, requires immediate initiation, adjustment, or addition of AHA thera

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Type 2 Diabetes Mellitus
MedDRA version: 18.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: MK-3102
Product Code: MK-3102
Pharmaceutical Form: Capsule
INN or Proposed INN: Omarigliptin
Current Sponsor code: MK-3102
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: MK-3102
Product Code: MK-3102
Pharmaceutical Form: Tablet
INN or Proposed INN: Omarigliptin
Current Sponsor code: MK-3102
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the impact of MK-3102 25 mg q.w. on:

a. the key secondary composite CV endpoint of confirmed CV-related death, nonfatal MI, or nonfatal stroke;
b. the time to first event for each of the following individual CV endpoints: confirmed CV-related death, MI (fatal + nonfatal), stroke (fatal + nonfatal), and unstable angina requiring hospitalization.
c. all-cause mortality;

To assess the effect of treatment with MK-3102 25 mg q.w. compared with placebo on fasting plasma glucose (FPG) at 4 months.

To assess the safety and tolerability of MK-3102 25 mg q.w.

To assess the impact of MK-3102 25 mg q.w. on:
a. The time to first event for each of the following individual CV endpoints: confirmed CV-related death, MI (fatal + nonfatal), and stroke (fatal + nonfatal);
b. All-cause mortality.

Main Objective: To assess the impact of MK-3102 25 mg q.w. on time to confirmed CV outcomes as measured by the time to first event in the CV composite endpoint of CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

To assess the effect of treatment with MK-3102 25 mg q.w. compared with placebo on A1C at 4 months.

To demonstrate the non-inferiority of MK-3102 (omarigliptin) compared with placebo (against a background of standard of care) on the time to first occurrence in the composite endpoint of cardiovascular death, nonfatal MI or non-fatal stroke.

Primary end point(s): Change from baseline in A1C and FPG

The primary composite CV endpoint, MACE plus, is comprised of CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

Timepoint(s) of evaluation of this end point: Various

Secondary Outcome(s)

Secondary end point(s): A key secondary endpoint, MACE, is comprised of CV-related death, nonfatal MI, and nonfatal stroke.

Timepoint(s) of evaluation of this end point: Various

Secondary ID(s)

2012-002414-39-HU

MK-3102-018

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 07/12/2017
• Date Completed: 22/03/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002414-39/results