Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)

NCT ID: NCT01971554

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-14
• Study Completion Date: 2014-04-26

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MK-8666 50 mg

MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14.

Group Type: EXPERIMENTAL

MK-8666

Intervention Type: DRUG

MK-8666, capsules, oral, QD, Days 1 to 14

Placebo

Intervention Type: DRUG

Placebo, capsules, oral, QD, Days 1 to 14

MK-8666 150 mg

MK-8666, 150 mg, oral, QD, for Days 1 to 14

Group Type: EXPERIMENTAL

MK-8666

Intervention Type: DRUG

MK-8666, capsules, oral, QD, Days 1 to 14

Placebo

Intervention Type: DRUG

Placebo, capsules, oral, QD, Days 1 to 14

MK-8666 500 mg

MK-8666, 500 mg, oral, QD for Days 1 to 14

Group Type: EXPERIMENTAL

MK-8666

Intervention Type: DRUG

MK-8666, capsules, oral, QD, Days 1 to 14

Placebo

Intervention Type: DRUG

Placebo, capsules, oral, QD, Days 1 to 14

Placebo

Placebo, oral, QD for Days 1 to 14

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, capsules, oral, QD, Days 1 to 14

Interventions

MK-8666

MK-8666, capsules, oral, QD, Days 1 to 14

Intervention Type: DRUG

Placebo

Placebo, capsules, oral, QD, Days 1 to 14

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 28727908 (View on PubMed)

Other Identifiers

8666-003

Identifier Type: -

Identifier Source: org_study_id