Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)
- Registration Number
- NCT01971554
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This is a study of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-8666 in participants with type 2 diabetes mellitus (T2DM). Participants enrolled in this trial would be either treatment-naive or have washed off of oral anti-hyperglycemic agents. MK-8666 is planned to be administered orally for up to 2 weeks. The primary hypothesis for this study is that after 14 days of once daily treatment with MK-8666, at a dose that is safe and well tolerated, the placebo-corrected fasting plasma glucose reduction from baseline is ≥34 mg/dL.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- If female, must be either postmenopausal or surgically sterile
- A Body Mass Index (BMI) ≥18 kg/m^2 to ≤40 kg/m^2, inclusive.
- A diagnosis of T2DM
- Drug naïve or is being treated with no more than 2 oral antihyperglycemic agents (thiazolidenediones are excluded)
- Judged to be in good health except for T2DM
- Willing to follow a standard weight maintaining diet throughout the study
- A nonsmoker or has not used nicotine or nicotine-containing products for at least 3 months
- A history of clinically significant endocrine (except T2DM), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
- A history of myositis or complaints including diffuse myalgias, muscle tenderness, or weakness.
- A history of cancer (malignancy) excepting adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix
- Has clinically unstable diabetic retinopathy, neuropathy, and/or clinical evidence of gastroparesis (frequent nausea, bloating or vomiting, severe gastroesophageal reflux, early satiety)
- A history of type 1 diabetes mellitus and/or history of ketoacidosis
- Taking a medication for a co-morbid condition that is not permitted during the study
- A history of significant multiple and/or severe allergies
- Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus
- Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to study participation
- Participated in another investigational trial within 4 weeks prior to study participation
- Consumes excessive amounts of alcoholic or caffeine-containing beverages
- A regular user of illicit drugs or a history of drug or alcohol abuse within the past year
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MK-8666 500 mg Placebo MK-8666, 500 mg, oral, QD for Days 1 to 14 Placebo Placebo Placebo, oral, QD for Days 1 to 14 MK-8666 50 mg Placebo MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14. MK-8666 150 mg Placebo MK-8666, 150 mg, oral, QD, for Days 1 to 14 MK-8666 50 mg MK-8666 MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14. MK-8666 150 mg MK-8666 MK-8666, 150 mg, oral, QD, for Days 1 to 14 MK-8666 500 mg MK-8666 MK-8666, 500 mg, oral, QD for Days 1 to 14
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced at Least Once Adverse Event Up to 28 days An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15 Predose (Baseline) and 24 h postdose Day 14 (Day 15) Blood glucose was measured on a fasting basis (collected after an 8-hour fast). Blood was collected on Day -1 (pre-planned dose), predose on Days 1, 3, 7, and 14, and 24h postdose Day 14 (Day 15). The baseline measurement was computed as the average of the Day -1 and predose Day 1 measurements. FPG is expressed as mg/dL. This change from baseline reflects values for Day 15 FPG minus Day 0 FPG values.
Number of Participants Who Discontinued Study Drug Due to an AE Up to 14 days An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
- Secondary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h) Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose AUC0-last is a measure of the total amount of drug in the plasma from the dose to 24 hours after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for AUC0-24h was geometric mean coefficient of variation percentage.
Maximum Plasma Drug Concentration After Dosing (Cmax) Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose Cmax is a measure of the maximum amount of drug in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for Cmax was geometric mean coefficient of variation percentage.
Time to Reach Cmax (Tmax) Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdose Tmax is a measure of the time to reach the maximum concentration in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group.
Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15 Baseline and Day 15 The 24h-WMG was considered to provide an integrated assessment of the glycemic exposure over the 24-hour period, and was derived from 18 blood samples collected immediately prior to, and after each meal, and overnight and fasting one hour pre-dose. A "weighted" rather than a "simple" mean is used to avoid overrepresentation of post-meal glucose values. On each day (Day -1 and Day 14), the WMG was computed as a time-weighted average of the 18 individual measurements.