- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01971554
Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)
August 10, 2018 updated by: Merck Sharp & Dohme LLC
A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
63
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MK-8666 50 mg
MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14.
|
MK-8666, capsules, oral, QD, Days 1 to 14
Placebo, capsules, oral, QD, Days 1 to 14
|
Experimental: MK-8666 150 mg
MK-8666, 150 mg, oral, QD, for Days 1 to 14
|
MK-8666, capsules, oral, QD, Days 1 to 14
Placebo, capsules, oral, QD, Days 1 to 14
|
Experimental: MK-8666 500 mg
MK-8666, 500 mg, oral, QD for Days 1 to 14
|
MK-8666, capsules, oral, QD, Days 1 to 14
Placebo, capsules, oral, QD, Days 1 to 14
|
Placebo Comparator: Placebo
Placebo, oral, QD for Days 1 to 14
|
Placebo, capsules, oral, QD, Days 1 to 14
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15
Time Frame: 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.
|
Predose (Baseline) and 24 h postdose Day 14 (Day 15)
|
Number of Participants Who Experienced at Least Once Adverse Event
Time Frame: 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.
|
Up to 28 days
|
Number of Participants Who Discontinued Study Drug Due to an AE
Time Frame: 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.
|
Up to 14 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Time Frame: 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.
|
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)
Time Frame: 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.
|
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)
Time Frame: 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.
|
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
Time Frame: 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.
|
Baseline and Day 15
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 14, 2013
Primary Completion (Actual)
April 26, 2014
Study Completion (Actual)
April 26, 2014
Study Registration Dates
First Submitted
October 14, 2013
First Submitted That Met QC Criteria
October 23, 2013
First Posted (Estimate)
October 29, 2013
Study Record Updates
Last Update Posted (Actual)
September 10, 2018
Last Update Submitted That Met QC Criteria
August 10, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 8666-003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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