| 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 24 weeks, to assess the effect of the addition of treatment with MK- 3102 compared to placebo on A1C.
- To assess the safety and tolerability of MK-3102. |
|
| E.2.2 | Secondary objectives of the trial |
- After 24 weeks, to assess the effect of the addition of treatment with
MK-3102 compared to placebo on 2-hour post-meal glucose (2-hour
PMG) after a standard meal challenge.
- After 24 weeks, to assess the effect of the addition of treatment with
MK-3102 compared to placebo on fasting plasma glucose (FPG).
- After 24 weeks, to assess the effect of the addition of treatment with
MK-3102 on the proportion of subjects achieving an A1C goal of <7.0%
(53 mmol/mol).
- After 24 weeks, to assess the effect of the addition of treatment with
MK-3102 on proportion of subjects achieving an A1C goal of <6.5% (48
mmol/mol).
- After 104 weeks, to assess the effect of the addition of treatment with
MK-3102 on (1) A1C; (2) FPG; (3) the durability of glycemic efficacy, and
(4) the proportion of subjects achieving an A1C goal (<7.0% [53
mmol/mol] and <6.5% [48 mmol/mol]). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject has T2DM, and must be ≥18 years of age on the day of signing
the informed consent form. Note: For India only: Subject has T2DM and
is ≥18 and ≤65 years of age on day of signing informed consent.
2. Subject is on metformin monotherapy at a stable dose of metformin
(≥1500 mg/day) for at least 12 weeks and has an A1C ≥7% (53
mmol/mol) and ≤10.5% (91 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 reached natural menopause (defined as ≥12 months of
spontaneous amenorrhea in women >45 years of age, or ≥6 months of
spontaneous amenorrhea with serum FSH levels in the postmenopausal
range as determined by the laboratory), or had a hysterectomy and/or
bilateral oophorectomy, or had bilateral tubal ligation at least 6 weeks
prior to screening.
c. Subject is a female of reproductive potential and:
1) Agrees to remain abstinent from heterosexual activity (this form of
birth control must be accepted by local regulatory agencies and ethics
review committees as the sole method of birth control).
OR
2) Agrees to use (or her partner to 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). |
|
| E.4 | Principal exclusion criteria |
1. Subject has a history of T1DM or a history of ketoacidosis OR Subject is assessed by the investigator as possibly having T1DM confirmed with
a C-peptide <0.7 ng/mL (0.23 nmol/L).
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, 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 ICF
5. Subject has a history of intolerance, hypersensitivity, or any other
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 or has planned major surgery during the trial.
8. Subject is on or likely to require treatment for ≥14 consecutive days or repeated courses of pharmacologic doses 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 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.
12. Subject has a medical history of active liver disease (other than non-alcoholic hepatic steatosis)
13. Subject has HIV as assessed by medical history.
14. Subject has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months
15. Subject has poorly controlled hypertension defined as systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥90 mm Hg and blood pressure is unlikely to be within these limits by Visit 2/Week -2 with an adjustment in antihypertensive medication.
16. 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.
17. Subject has a clinically important hematological disorder
18. Subject has exclusionary laboratory values as listed in in the protocol.
19. Subject has a positive urine pregnancy test.
20. 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.
21. Subject is, at the time of signing ICF a user of recreational or illicit drugs or has had a recent history of drug abuse.
22. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
23. Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that makes participation not in the subject’s best interest.
24. 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 subject has received, or is anticipated to receive, blood products within 12 weeks of signing informed consent or within the projected duration of the trial.
25. Subject is unlikely to adhere to the trial procedures, keep appointments, or is planning to relocate during the trial.
26. 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 >260 mg/dL (14.4 mmol/L).
27 Subject has a clinically significant ECG abnormality which in the opinion of the investigator exposes the subject to risk by enrolling in the trial.
28. Subject has poorly controlled hypertension
29. Subject is on lipid-lowering medication or thyroid replacement therapy, and has not been on a stable therapy for the 4 weeks, or 6 weeks prior to Visit 3/Day 1. 29.
30 Subject has a positive urine pregnancy test (to be performed before randomization of the subject).
31. Subject has a site FFSG >250 mg/dL (13.8 mmol/L).
32. Subject has developed a new medical condition, suffered a change in status of an established medical condition, demonstrated a laboratory or ECG abnormality, or required a new treatment or medication during the pre-randomization period which meets any previously described trial exclusion 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 at Week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Change from baseline in 2-hour post meal glucose (PMG) at Week 24;
- Change from baseline in FPG at Week 24.
- Change from baseline in A1C at Week 104;
- Change from baseline in FPG at Week 104;
- Proportion of subjects attaining A1C glycemic goals of <7% and <6.5% after 24 and 104 weeks of treatment;
- Change from baseline in post-meal glucose total AUC at Week 24;
- Change from baseline in fasting insulin at Week 24 and Week 104;
- Time to rescue over 24 and 104 weeks;
- Proportion of subjects requiring rescue therapy at Week 24 and 104.
- Safety Endpoints |
|
| 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 | Yes |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 |
| European Union |
| Mexico |
| Russian Federation |
| South Africa |
| United States |
|
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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