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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01971554
First received: October 14, 2013
Last updated: October 14, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: MK-8666
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Type 2 Diabetes Mellitus Patients

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15 [ Time Frame: Predose (Baseline) and 24 h postdose Day 14 (Day 15) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Experienced at Least Once Adverse Event [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 14 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15 [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
    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.


Enrollment: 63
Study Start Date: October 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8666 50 mg
MK-8666, 50 mg, oral, once a day (QD) for Days 1 to 14.
Drug: MK-8666
MK-8666, capsules, oral, QD, Days 1 to 14
Drug: Placebo
Placebo, capsules, oral, QD, Days 1 to 14
Experimental: MK-8666 150 mg
MK-8666, 150 mg, oral, QD, for Days 1 to 14
Drug: MK-8666
MK-8666, capsules, oral, QD, Days 1 to 14
Drug: Placebo
Placebo, capsules, oral, QD, Days 1 to 14
Experimental: MK-8666 500 mg
MK-8666, 500 mg, oral, QD for Days 1 to 14
Drug: MK-8666
MK-8666, capsules, oral, QD, Days 1 to 14
Drug: Placebo
Placebo, capsules, oral, QD, Days 1 to 14
Placebo Comparator: Placebo
Placebo, oral, QD for Days 1 to 14
Drug: Placebo
Placebo, capsules, oral, QD, Days 1 to 14

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01971554

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01971554     History of Changes
Other Study ID Numbers: 8666-003 
Study First Received: October 14, 2013
Results First Received: October 14, 2016
Last Updated: October 14, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on December 09, 2016