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: 10 July 2015
• Main ID: EUCTR2012-002309-23-PL
• Date of registration: 27/02/2013
• 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: 27/05/2013
• Target sample size: 748
• 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 711
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 37

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
V1/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 past 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 ICF.
23. Subject is unlikely to

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: 18.0 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)

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.

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.

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.