| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067585 |
| E.1.2 | Term | Type 2 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
After 54 weeks, to assess the A1C-lowering efficacy of MK-3102 compared to glimepiride.
To assess the safety and tolerability of MK-3102. |
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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). |
|
| E.4 | Principal 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 adhere to the trial procedures keep
appointments or is planning to relocate during the trial.
24. Subject has symptomatic hyperglycemia that in the investigator's
opinion requires immediate initiation, adjustment, or addition of
antihyperglycemic therapy or has a fasting plasma glucose consistently
25. Subject has a clinically significant ECG abnormality which in the
opinion of the investigator exposes the subject to risk by enrolling in the
trial.
26. Subject has poorly controlled hypertension defined as systolic blood
pressure of ≥160 mm Hg or diastolic blood pressure of ≥90 mm Hg.
27. Subject is on lipid-lowering medication or thyroid replacement
therapy, and has not been on a stable therapy for the 4 weeks (lipidlowering
medication), or 6 weeks (thyroid replacement therapy) prior to
V3/Day 1. In this case the current visit can be changed to an
Unscheduled Visit.
28. Subject has a positive urine pregnancy test (at randomisation)
29. Subject has a site fasting-fingerstick glucose <126 mg/dL or >260
mg/dL.
30. Subject has developed a new medical condition, suffered a change of
an established medical condition, developed a lab or ECG abnormality, or
required a new treatment or medication during the pre-randomization
period which meets any previously described trial exc. criteria or which,
in the opinion of the investigator, exposes the subject to risk by
enrolling in the trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change from baseline in A1C
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Croatia |
| European Union |
| India |
| Israel |
| Korea, Republic of |
| Lebanon |
| Malaysia |
| Mexico |
| Russian Federation |
| United States |
| Jordan |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
