E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency |
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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 | 17.1 |
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 |
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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 treatment with MK-3102 compared with placebo on A1C.
To assess the safety and tolerability of MK-3102. |
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E.2.2 | Secondary objectives of the trial |
(1) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 compared with placebo on FPG.
(2) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 on proportion of subjects achieving an A1C goal of <7.0% (53mmol/mol).
(3) Objective: After 54 weeks, to assess the effect of treatment with MK-3102 on proportion of subjects achieving an A1C goal of <7.0% (53mmol/mol).
(4) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 compared with placebo on 2-hour Post-Meal Glucose (PMG).
(5) Objective: After 54 weeks, to assess the effect of treatment with MK-3102 on A1C and FPG.
6) Objective: After 24 weeks, and after 54 weeks, to assess the effect of treatment with MK-3102 on proportion of subjects achieving an A1C goal of <6.5% (48 mmol/mol) |
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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 (for India: ≥18 and ≤65 years of age) on the day of signing the informed consent form.
2. Subject meets one of the following criteria:
a. Subject is currently not on an AHA (off AHA therapies for ≥12 weeks) and has a Visit 1/Screening Visit A1C ≥7.0 and ≤10.0%.
b. Subject is currently on a stable dose for > 12 weeks of a single AHA or low-dose dual oral AHA
combination therapy (i.e., ≤50% maximum labeled dose of each agent [except thiazolidinediones (TZDs)]) and has a Visit 1/ Screening Visit A1C ≥6.5 and ≤9.0% AND based upon review of the
subject’s current diet, medical regimen, and Visit 1 A1C, subject is considered by the investigator
to be likely to meet Visit 3/Week -2 inclusion criterion of A1C ≥7.0 and ≤10.0% AFTER the 8-week
wash-off period prior to Visit 3/Week-2 (Visit 2/Week -10 to Visit 3/ Week -2).
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 follicular stimulating hormone [FSH] levels in the postmenopausal range as determined by the laboratory), or
• 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 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
• 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, 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 an A1C of ≥7.0% and ≤10.0% within 2 weeks of Visit 3/Week -2.
Note: If the A1C is not within the Visit 3 A1C inclusion criterion, a single repeat measurement
maybe performed at the discretion of the investigator. If repeat value meets Visit 3 A1C inclusion criterion, subject may continue in the trial.
6. Subject has 100% compliance with MK-3102 placebo treatment during the single-blind run-in period (as determined by site-performed capsule count).
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E.4 | Principal exclusion criteria |
1.Subject has a history of type 1 diabetes mellitus or a history of ketoacidosis or is assessed by the investigator as possibly having type 1 diabetes confirmed with a C-peptide <0.7 ng/mL (0.23 nmol/L)
2.has been treated with:
a.thiazolidinedione (TZD) within 4 months of signing informed consent, or
b.GLP-1 receptor mimetic or agonist or DPP-4 inhibitors within 6 months of signing informed consent, or
c.insulin or sodium-glucose cotransporter (SGLT2) inhibitor within 12 weeks prior to signing informed consent
d.MK-3102 at any time prior to signing informed consent
3.has a history of hypersensitivity to a DPP-4 inhibitor
4.is currently participating in/has participated in another trial with an investigational compound or device within the prior 12 weeks of signing the informed consent and does not agree to refrain from participating in any other trial
5.has a history of intolerance,hypersensitivity or any contraindication to metformin (in Phase A),glimepiride or other sulfonyurea (in Phase B)
based upon the label in the country of the investigational site
6.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.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.is currently being treated for hyperthyroidism or subject is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
10.is currently on or likely to require treatment with a prohibited medication
11.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.has a medical history of active liver disease,including chronic active hepatitis B or C,primary biliary cirrhosis, or symptomatic gallbladder disease
13.has HIV as assessed by medical history
14.has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months,or has any of the following disorders within the past 3 months:
a.Acute coronary syndrome
b.Coronary artery intervention
c.Stroke or transient ischemic neurological disorder
15.has poorly controlled hypertension defined as systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥90 mm Hg
16.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.has a clinically important hematological disorder
18.has exclusionary laboratory values (as per protocol)
19.has a positive urine pregnancy test
20.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.is a user of recreational or illicit drugs or has had a recent history of drug abuse
22.routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week,or engages in binge drinking
23.has a history or current evidence of any condition that makes participation not in the subject's best interest
24.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 duration of the trial
25.is unlikely to adhere to the trial procedures or is planning to relocate during the trial
26.has symptomatic hyperglycemia that requires immediate initiation,adjustment,or addition of antihyperglycemic therapy or has a fasting plasma glucose consistently
27.has a clinically significant ECG abnormality which exposes the subject to risk by enrolling in the trial
28.has a fasting plasma glucose consistently
29.has poorly controlled hypertension defined as systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥90 mm Hg
30.is on lipid-lowering medication or thyroid replacement therapy,and has not been on a stable regimen for the 4 weeks (lipid-lowering
medication),or 6 weeks (thyroid replacement therapy) prior to Visit 4/Day 1
31.has a positive urine pregnancy test
32.has a site-fasting-fingerstick glucose (FFSG) >260 mg/dL (>14.4 mmol/L)
33.has developed a new medical condition/change in status of an established medical condition,developed a laboratory or ECG
abnormality,or required a new treatment or medication during the prerandomization 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
A1C – Change from baseline at Week 24
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in fasting plasma glucose (FPG) at Week 24
- Proportion of subjects attaining A1C glycemic goals of <7% (53
mmol/mol) after 24 weeks of treatment
- Proportion of subjects attaining A1C glycemic goals of <7% (53
mmol/mol) after 54 weeks of treatment
- Change from baseline in 2-hour post meal glucose (PMG) at Week 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks (54 weeks for the third secondary end point) |
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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) | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Bulgaria |
Germany |
Hungary |
India |
Italy |
Korea, Republic of |
Philippines |
Romania |
Taiwan |
United Kingdom |
United States |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 17 |