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

NCT01971554 | Completed Phase 1 Results

• 1 other identifier: 8666-003
• Study Type: interventional
• Target: 63
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Fasting Plasma Glucose (FPG) at 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.

  Predose (Baseline) and 24 h postdose Day 14 (Day 15)

• Number of Participants Who Experienced at Least Once Adverse Event

  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.

  Up to 28 days

• Number of Participants Who Discontinued Study Drug Due to an AE

  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.

  Up to 14 days

Secondary Outcomes (4)

• 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

• 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

• 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

• Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15

  Baseline and Day 15

Study Arms (4)

MK-8666 50 mg

EXPERIMENTAL

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

Drug: MK-8666; Drug: Placebo

MK-8666 150 mg

EXPERIMENTAL

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

Drug: MK-8666; Drug: Placebo

MK-8666 500 mg

EXPERIMENTAL

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

Drug: MK-8666; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo, oral, QD for Days 1 to 14

Drug: Placebo

Interventions

MK-8666 DRUG

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

MK-8666 150 mg; MK-8666 50 mg; MK-8666 500 mg

Placebo DRUG

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

MK-8666 150 mg; MK-8666 50 mg; MK-8666 500 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 28727908 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: October 29, 2013
• Study Start: October 14, 2013
• Primary Completion: April 26, 2014
• Study Completion: April 26, 2014
• Last Updated: September 10, 2018
• Results First Posted: December 8, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share