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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01971554
• Other study ID #: 8666-003
• Status: Completed
• Phase: Phase 1
• Start date: October 14, 2013
• Est. completion date: April 26, 2014

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: April 26, 2014
• Est. primary completion date: April 26, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• MK-8666
MK-8666, capsules, oral, QD, Days 1 to 14
• Placebo
Placebo, capsules, oral, QD, Days 1 to 14

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)	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.	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
Secondary	Maximum Plasma Drug Concentration After Dosing (Cmax)	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.	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
Secondary	Time to Reach Cmax (Tmax)	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.	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
Secondary	Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at 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.	Baseline and Day 15