Clinical trial NCT01971554: Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)
Official title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-10-29
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15
timeFrame: Predose (Baseline) and 24 h postdose Day 14 (Day 15)
measure: Number of Participants Who Experienced at Least Once Adverse Event
timeFrame: Up to 28 days
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 14 days
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
timeFrame: 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
measure: Maximum Plasma Drug Concentration After Dosing (Cmax)
timeFrame: 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
measure: Time to Reach Cmax (Tmax)
timeFrame: 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
measure: Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15
timeFrame: Baseline and Day 15
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Krug AW, Vaddady P, Railkar RA, Musser BJ, Cote J, Ederveen A, Krefetz DG, DeNoia E, Free AL, Morrow L, Chakravarthy MV, Kauh E, Tatosian DA, Kothare PA. Leveraging a Clinical Phase Ib Proof-of-Concept Study for the GPR40 Agonist MK-8666 in Patients With Type 2 Diabetes for Model-Informed Phase II Dose Selection. Clin Transl Sci. 2017 Sep;10(5):404-411. doi: 10.1111/cts.12479. Epub 2017 Jul 20.