A Phase IIA, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of MK-8245 in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control

Phase 1

Conditions: Type 2 Diabetes Mellitus
MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus

Registration Number: EUCTR2008-005817-23-PL

Lead Sponsor: Merck & Co., Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 76

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-? 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 PPAR? 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).
•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 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 dry eye syndrome, or has any condition that may predispose to dry eye condition (e.g., lupus, rheumatoid arthritis, etc.).
•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 T

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: (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.<br> (2) After 4 weeks of treatment, to assess the safety and tolerability of MK-8245.<br> ;<br> Secondary Objective: (1) After 4 weeks of treatment, to assess the effect of MK-8245 compared to placebo on change in fasting plasma glucose from baseline.<br> (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<br> ;Primary end point(s): 24-hour Weighted Mean Glucose

Secondary Outcome Measures

Name	Time	Method

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