| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
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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 |
(1) After 4 weeks of treatment, to assess the effect of MK-8245 compared to placebo on 24-hour Weighted Mean Glucose (24h-WMG) from baseline.
(2) After 4 weeks of treatment, to assess the safety and tolerability of MK-8245. |
|
| E.2.2 | Secondary objectives of the trial |
(1) After 4 weeks of treatment, to assess the effect of MK-8245 compared to placebo on change in fasting plasma glucose from baseline.
(2) To obtain preliminary plasma pharmacokinetics (e.g. concentration of drug in the plasma at trough [C12hr]) after oral administration of multiple doses of MK-8245 to patients with type 2 diabetes mellitus |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Patient has type 2 diabetes mellitus (T2DM).
•Patient is ≥ 18 and ≤ 65 years of age on day of signing informed consent.
•Patient has body mass index (BMI) > 27 kg/m2 and < 43 kg/m2.
•Patient meets one of the following criteria as indicated by a "yes" answer to one of the following:
1) patient is drug naïve or currently not on AHA (off AHA for ≥ 12 weeks), and has Visit 1 / Screening Visit A1C ≥ 7% and ≤ 10% OR
2) patient is currently on single AHA and has Visit 1 / Screening Visit A1C ≥ 7% and ≤ 9.5% OR
3) patient is currently on low dose, oral AHA combination therapy (i.e., ≤ 50% maximum labeled dose of each agent) and has a Visit 1 / Screening Visit A1C ≥ 6.5% and ≤ 9.5%
NOTE: Patients who at Visit 1 are on PPAR-γ agents (i.e., TZDs), either as monotherapy or in combination therapy with other AHA, are not allowed to participate in the study.
•Patient is a male, or female without reproductive potential. A female patient who is not of reproductive potential is defined as one who has either
4) reached natural menopause (defined as ≥ 6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the central laboratory, or ≥ 2 years of spontaneous amenorrhea in woman > 45 years of age.
5) undergone post surgical bilateral oophorectomy and/or hysterectomy,
6) undergone a bilateral tubal ligation.
•Patient has an FPG ≥ 130 mg/dL (7.2 mmol/L) and ≤ 260 mg/dL (14.4 mmol/L).
NOTE: If Visit 3 FPG does not meet this criterion AND is not consistent with the patient's recent fasting SBGM values, a single repeat measurement may be performed at the discretion of the Investigator. If the repeat value meets FPG inclusion criterion, patient may continue in the study.
•Patient has successfully completed the 24-hour domicile procedures which includes consuming ≥ 50% of each meal based on caloric content.
NOTE: If the patient does not meet this inclusion criterion and it is the Investigator's opinion that the patient is likely to meet this criterion during a second attempt, the current visit can be changed to an "unscheduled visit", and the patient can be rescheduled for Visit 4/Day -1 within one week, and be randomized only if the repeat 24-hour domicile procedures are completed successfully.
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| E.4 | Principal exclusion criteria |
•History of type 1 diabetes mellitus or a history of ketoacidosis, or patient is assessed by the investigator as possibly having type 1 diabetes confirmed with a C -peptide < 0.7 ng/mL (< 0.23 nmol/L).
•Has been treated with PPARγ agent (i.e., TZD [pioglitazone or rosiglitazone]) or with insulin therapy within the past 12 weeks.
•Has been treated with lipid lowering medications such as statins (i.e., HMG-CoA reductases [e.g., simvastatin, atorvastatin]), fibrates (e.g., gemfibrozil, fenofibrate), ezetimibe, niacin, or bile acid sequestrants within the prior 4 weeks.
•Has been on a weight loss program and is not in the maintenance phase, or patient started weight loss medication (e.g., orlistat, rimonabant, sibutramine, etc.) within the prior 12 weeks.
•Is being treated with immunosuppressive or immunomodulating agents (e.g., methotrexate, cyclosporine, etanercept), or patient is on, or is likely to require treatment with pharmacological doses of corticosteroids, or is on physiologic replacement therapy with oral corticosteroids (i.e., patient with adrenal insufficiency).
•Is currently participating in a study, or has participated in a study with or without an investigational compound or device within the prior 12 weeks of signing informed consent.
•Has undergone a surgical procedure within 30 days prior to signing informed consent or has planned major surgery.
•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), cirrhosis, or symptomatic gallbladder disease.
•Has history of coronary heart disease or congestive heart failure.
•Had stroke or transient ischemic neurological disorder within the past 6 months.
•Has severe peripheral vascular disease (e.g., manifested by claudication with minimal activity, a non-healing ischemic ulcer, or disease which is likely to require intervention such as with bypass or angioplasty).
•Has a systolic blood pressure > 160 mm Hg or diastolic > 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.
•Has a clinically important hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
•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. Patient with a history of malignancy > 5 years prior to signing informed consent should have no evidence of disease.
•Has a history of macular edema or vitreous hemorrhage.
•Has a recent history (i.e., within prior two weeks) of eye infection or another inflammatory condition of the eye or conjunctiva, including uveitis or scleritis.
•Has a history of contact lens use within the prior 3 months.
•Has dry eye syndrome, or has any condition that may predispose to dry eye condition (e.g., lupus, rheumatoid arthritis, etc.).
•Has used medicated eye drops within the prior 4 weeks.
•Has exclusionary lab values as described in the protocol.
•Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
•Has known allergies or intolerance to ingredients of the meals provided during the 24-hour domicile visit.
•Is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
•Has poor mental function or any other reason to expect that the patient may have difficulty in complying with the requirements of the study.
•Has finding of dry eye (i.e., wetting values < 5 mm in 5 minutes assessed by Schirmer test), or evidence of eye infection or other inflammatory condition of the eye or conjunctiva, or presence of superficial punctuate keratitis at the ophthalmologic examination.
•Has clinically significant abnormalities of electrocardiogram, including but not limited to, prolonged QTc interval (i.e., > 480 ms).
•Has LDL cholesterol > 160 mg/dL (1.8 mmol/L) or total TG > 500 mg/dL (5.7 mmol/L).
•Has a site fasting fingerstick glucose of < 130 mg/dL (7.2 mmol/L) or > 260 mg/dL (14.4 mmol/L).
•Developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory abnormality, or required a new treatment or medication during the run-in which meets any previously described study exclusion criterion.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| 24-hour Weighted Mean Glucose |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.3 |
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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 | Information not present in EudraCT |
| 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 |
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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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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