Type 2 Diabetes Mellitus

Primary (1) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 compared with placebo on A1C. (2) Objective: To assess the safety and tolerability of MK-3102. 2.1.2 Secondary (1) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 compared with placebo on 2-hour Post-Meal Glucose (PMG). (2) Objective: After 24 weeks, to assess the effect of treatment with MK-3102 compared with placebo on FPG. (3) Objective: After 54 weeks, to assess the effect of treatment with MK-3102 on A1C, 2-hour PMG, and FPG. (4) 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 (<6.5%, <7.0%).

MK-3102

MK-3102

capsule

25mg/cap

Primary Endpoint
Change from baseline in A1C at Week 24
Key Secondary Endpoints
Change from baseline in 2-hour post meal glucose (PMG) at Week 24
Change from baseline in fasting plasma glucose (FPG) at Week 24
Other Secondary Endpoints
Change from baseline in A1C at Week 54
Change from baseline in 2-hour post meal glucose (PMG) at Week 54
Change from baseline in fasting plasma glucose (FPG) at Week 54
Proportion of patients attaining A1C glycemic goals of <7% and <6.5% after 24
weeks of treatment
Proportion of patients attaining A1C glycemic goals of <7% and <6.5% after 54
weeks of treatment
Change from baseline in MTT at Week 24
Change from baseline in HOMA-beta at Week 24
Change from baseline in HOMA-IR at Week 24

All laboratory measurements are to be performed after an overnight fast ≥10 hours in
duration. Subjects with laboratory screening values/findings not meeting protocol
inclusion criteria may, at the discretion of the investigator, have one repeat determination
performed by the central laboratory. If the repeat value satisfies the criterion they may
continue in the screening process. Only laboratory tests not meeting inclusion criteria are
to be repeated (not the entire panel).
Subjects must meet all of the following criteria to participate in the trial.
At Visit 1/Screening
1. Subject has T2DM and must be ≥18 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 FSH levels in the postmenopausal range as
determined by the laboratory), or
• had bilateral oophorectomy and/or hysterectomy, or had bilateral tubal
ligation at least 6 weeks prior to screening
c. Subject is a female of reproductive potential and agrees to:
• remain abstinent from heterosexual activity (this form of birth control must
be accepted by local regulatory agencies and review committees as the sole
method of birth control), or
• use (or have their partner use) adequate contraception to prevent pregnancy
within the projected duration of the trial and for 21 days after the last dose
of trial medication. Adequate methods of contraception include:
o use of 2 barrier methods. Acceptable barrier methods are:
diaphragm with spermicide, cervical cap, contraceptive sponge,
condom
o use of an IUD and one of the barrier methods identified above
o vasectomy in a male partner and use of one of the barrier methods
identified 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.
At Visit 3/Week -2
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.
At Visit 4/Randomization
6. Subject has 100% compliance with MK-3102 placebo treatment during the single-blind
run-in period (as determined by site-performed capsule count).

All laboratory measurements are to be performed after an overnight fast ≥10 hours in
duration. Subjects with laboratory screening values/findings meeting protocol exclusion
criteria may, at the discretion of the investigator, have one repeat determination performed
by the central laboratory. If the repeat value does not meet the criterion, the subject may
continue in the screening process. Only laboratory tests meeting exclusion criteria are to
be repeated (not the entire panel).
Subjects must be excluded if they meet any of the following criteria.
At Visit 1/Screening
1. Subject has a history of type 1 diabetes mellitus or a history of ketoacidosis.
OR
Subject is assessed by the investigator as possibly having type 1 diabetes confirmed
with a C-peptide <0.7 ng/mL (0.23 nmol/L). Note: Only subjects assessed by the
investigator as possibly having type 1 diabetes should have C-peptide measured at
Visit 1/Screening.
2. Subject has been treated with:
a. a thiazolidinedione (TZD) within 4 months of signing informed consent, or
b. a GLP-1 receptor mimetic or agonist (such as exenatide or liraglutide) or DPP-4
inhibitors within 6 months of signing informed consent, or
c. insulin within 12 weeks prior to signing informed consent.
Note: A subject who has received a brief period of insulin treatment (such as few
days during a hospitalization) and who is no longer requiring insulin treatment
may participate.
3. Subject has a history of hypersensitivity to a DPP-4 inhibitor.
Subjects Requiring Specific Treatments
4. Subject is currently participating in or 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 while
participating in this trial.
Note: A subject who has participated in a non-interventional trial may be enrolled.
5. Subject has a history of intolerance, hypersensitivity or any contraindication to
metformin (in Phase A) and glimepiride or other sulfonyurea (in Phase B) 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 or has started
a weight loss medication 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.
Note: A subject who has undergone minor surgery within the prior 4 weeks and is
fully recovered or a subject who has planned minor surgery may participate. Minor
surgery is defined as a surgical procedure involving local anesthesia.
8. Subject is on or likely to require treatment for ≥2 consecutive weeks or repeated
courses of pharmacologic doses of corticosteroids.
Note: inhaled, nasal, and topical corticosteroids are permitted.
9. Subject 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. Subject is currently on or likely to require treatment with a prohibited medication (see
Section 3.2.1.2 for a list of prohibited medications).
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 trial medication.
Concomitant Disease of Organs and Systems
12. Subject has a medical history of active liver disease (other than non-alcoholic hepatic
steatosis), including chronic active hepatitis B or C (assessed by medical history),
primary biliary cirrhosis, or symptomatic gallbladder disease.
13. Subject has human immunodeficiency virus (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, or has any of the following disorders
within the past 3 months:
a. Acute coronary syndrome (e.g., MI or unstable angina)
b. Coronary artery intervention (e.g., CABG or PTCA)
c. Stroke or transient ischemic neurological disorder
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 not
considered likely to be under these limits by Visit 3/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.
Note:
• A subject with a history of malignancy >5 years prior to signing informed consent
should have no evidence of residual or recurrent disease
• A subject with any history of melanoma, leukemia, lymphoma, or renal cell
carcinoma is excluded.
17. Subject has a clinically important hematological disorder (such as aplastic anemia,
myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
Exclusion Criteria Based on Laboratory Abnormalities
18. Subject has exclusionary laboratory values as listed in Table 2-1 below.
Other Criteria
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 trial medication.
21. 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.
22. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per
week, or engages in binge drinking.
Note (1): One alcoholic drink is defined as 5 oz (150 mL) of wine, or 12 oz (350 mL)
of beer, or 1.5 oz (50 mL) of 80-proof liquor.
Note (2): Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male),
or 4 or more alcoholic drinks (female) in about 2 hours.
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,
• might interfere with the subject’s participation for the full duration of the trial,
• might confound the results of the trial.
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.