A study to evaluate the safety and efficacy of the addition of a new drug (MK-3102) compared with the addition of a licensed drug (Glimepiride) in patients with Type 2 Diabetes.

• Register: EUCTR
• Last refreshed on: 7 April 2015
• Main ID: EUCTR2012-002309-23-DE
• Date of registration: 31/10/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: A study to evaluate the safety and efficacy of the addition of a new drug (MK-3102) compared with the addition of a licensed drug (Glimepiride) in patients with Type 2 Diabetes.
• Scientific title: A Phase III, Multicenter, Double-Blind, Randomized Study to Evaluate the Safety and Efficacy of the Addition of MK-3102 Compared With the Addition of Glimepiride in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin
• Date of first enrolment: 22/03/2013
• Target sample size: 680
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002309-23
• 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: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Croatia, European Union, Germany, Hungary, India, Israel, Jordan, Korea, Republic of, Lebanon, Lithuania, Malaysia, Mexico, Poland, Russian Federation, 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. Subject has T2DM and must be =18 of age on the day of signing the informed consent form. For India: subject has T2DM and is =18 and =65 years of age.

2. Subject is on a stable dose of metformin (=1500 mg/day) for at least 12 weeks with inadequate glycemic control, i.e., A1C =6.5% (48 mmol/mol) and =9.0% (75 mmol/mol).

3. Subject 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 6 weeks prior to screening.
c. Subject is a female of reproductive potential and:
(1) agrees to remain abstinent from heterosexual activity (if this form of birth control is accepted by local regulatory agencies and ethics review committees as the sole method of birth control), or
(2) agrees to use (or have their partner use) acceptable contraception to prevent pregnancy within the projected duration of the trial and for 21 days after the last dose of blinded study medication. Two methods of contraception will be used to avoid pregnancy. Acceptable combinations of methods include:
- Use of one of the following double-barrier methods: diaphragm with spermicide and a condom; cervical cap and a condom; or contraceptive sponge and a condom.
- Use of hormonal contraception (any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent [including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous patch]) with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; vasectomy; or (intrauterine device) IUD.
- Use of an IUD with one of the following: condom; diaphragm with spermicide; contraceptive sponge; vasectomy; or hormonal contraception (see above).
-Vasectomy with one of the following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; IUD; or hormonal contraception (see above).

4. Subject understands the trial procedures, alternative treatments available, and risks involved with the trial, and voluntarily agrees to participate by giving written informed consent. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.

5. Subject has 100% compliance with MK-3102 placebo treatment during the single blind run-in period (as determined by site performed capsule count).

AND
Subject has 85% compliance with glimepiride placebo treatment during the singleblind run-in period (as determined by site performed capsule count).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 646
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion criteria:
1. Subject has a history of T1DM or a history of ketoacidosis. OR is assessed by the investigator as possibly having T1DM confirmed with a C-peptide <0.7 ng/mL
2. Subject has been treated with any AHA therapies other than the protocol-required metformin within the prior 12 weeks of Visit 1/Screening or with MK-3102 at any time prior to signing informed consent.
3. Subject has a history of hypersensitivity to a DPP-4 inhibitor.
4. Subject is currently participating in, or has participated, in a trial in which the subject received an investigational compound or used an investigational device within the prior 12 weeks of signing the informed consent
5. Subject has a history of intolerance or hypersensitivity to glimepiride, or insulin glargine or any contraindication to metformin, glimepiride, or insulin glargine based upon the label in the country of the investigational site.
6. Subject is on a weight loss program and is not in the maintenance phase; has been on a weight loss medication in the last 6 months; or has undergone bariatric surgery within 12 months prior to signing the informed consent.
7. Subject has undergone a surgical procedure within 4 weeks prior to signing informed consent
8. Subject is on or likely to require treatment for =14 consecutive days or repeated courses of corticosteroids.
9. Subject is currently being treated for hyperthyroidism or subject is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks.
10. Subject is currently on or likely to require treatment with a prohibited medication
11. Subject has a medical history of active liver disease including chronic active hepatitis B or C primary biliary cirrhosis, or symptomatic gallbladder disease.
12. Subject has HIV as assessed by medical history.
13. Subject has had new or worsening signs or symptoms of CHD or CHF within the past 3 months, or has any of the following disorders within the past 3 months: Acute coronary syndrome, Coronary artery intervention, Stroke or transient ischemic neurological disorder
14. Subject has poorly controlled hypertension and blood pressure is unlikely to be within these limits by Visit 2/Week -2 with an adjustment in antihypertensive medication.
15. Subject has a 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.
16. Subject has a clinically important hematological disorder
17. Subject has exclusionary laboratory values as listed in protocol
18. Subject has a positive urine pregnancy test (At screening)
19. 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 Subject 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.
20. 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. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
21. Subject has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that makes participation not in the subject’s best interest
22. Subject has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing in

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: 16.1 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

Trade Name: Glimepiride
Product Name: Glimepiride
Pharmaceutical Form: Tablet
INN or Proposed INN: GLIMEPIRIDE
CAS Number: 93479-97-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Glimepiride
Product Name: Glimepiride
Pharmaceutical Form: Tablet
INN or Proposed INN: GLIMEPIRIDE
CAS Number: 93479-97-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: After 54 weeks, to assess the A1C-lowering efficacy of MK-3102 compared to glimepiride.

To assess the safety and tolerability of MK-3102.

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

Secondary Objective: After 54 weeks, to assess the effect of the addition of MK-3102 compared with glimepiride on the incidence of symptomatic hypoglycemia.

After 54 weeks, to assess the effect of the addition of MK-3102 compared with glimepiride on gain in body weight from baseline.

After 54 weeks, to assess the effect of the addition of MK-3102 compared with glimepiride on fasting plasma glucose (FPG).

After 54 weeks, to assess the effect of the addition of MK-3102 compared with glimepiride on proportion of subjects achieving an A1C goal (<6.5% [48 mmol/mol], <7.0% [53 mmol/mol]).

After 54 weeks, to assess the effect of the addition of MK-3102 compared with glimepiride on durability of glycemic efficacy.

After 54 weeks, to assess the effect of MK-3102 versus glimepiride on the proportion of subjects meeting the composite endpoint of an A1C decrease >0.5% with no symptomatic hypoglycemia and no body weight gain.

Timepoint(s) of evaluation of this end point: Week 54

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 54

Secondary end point(s): - Change from baseline in FPG
- Proportion of subjects achieving the goal A1C <6.5% (48 mmol/mol), <7.0% (53 mmol/mol) at Week 54.
- Proportion of subjects with AE of symptomatic hypoglycemia up to Week 54;
- Change from baseline in body weight at Week 54.

Secondary ID(s)

2012-002309-23-HU

MK-3102-016

Source(s) of Monetary Support

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