A Multiple-Dose Study of MK-1006 (MK-1006-004)(TERMINATED)

A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1006.

This study will asses the safety, tolerability, multiple-dose pharmacokinetics and pharmacodynamics of MK1006 in participants with type 2 diabetes.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: MK-1006; Drug: Comparator: Placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Participation Criteria

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:

• Participant has a BMI less than or equal to 42 kg/m^2 at the screening visit
• Participant has been diagnosed with Type 2 Diabetes that is being treated either by diet and exercise alone or by single or combination oral anti-hyperglycemic medications
• Participant is willing to follow a diet containing approximately 50% carbohydrates, 20% protein, and 30% fat during the study
• Participant is a nonsmoker and has not used nicotine containing products for ~ 6 months before start of study

Exclusion Criteria:

• Participant must not be treated with three or more oral anti-hyperglycemic medications, insulin, or PPAR-gamma agonists
• Participant has a history of stroke, chronic seizures, or a major neurological disorder
• Participant has had an eye infection or other inflammatory eye condition within 2 weeks of first dose of study drug
• Participant has glaucoma or is blind
• Participant has a condition known to be related to cataract development
• Participant has had or will have incisional eye surgery within 6 months before screening or has had laser surgery (other than Lasik) within 3 months of screening
• Participant has a history of type 1 diabetes or ketoacidosis
• Participant cannot stop taking certain current medications during the study
• Participant consumes greater than 3 alcoholic beverages per day
• Participant consumes more than 6 servings of caffeinated beverages per day (1 serving is ~ 120 mg caffeine)
• Participant has a history of significant multiple or severe allergies or has had a reaction to or is intolerant of prescription/non-prescription drugs or food
• Participant uses recreational drugs or has had a history of drug abuse within 6 months of start of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1006 20 mg Once Daily (Panel A); After a 2-week run-in/wash-off period, participants received single daily doses (q.d.) of 20 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the Clinical Research Unit (CRU).	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 40 mg Once Daily (Panel B); After a 2-week run-in/wash-off period, participants received single daily doses of 40 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 80 mg Once Daily (Panel C); After a 2-week run-in/wash-off period, participants received single daily doses of 80 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 120 mg Once Daily (Panel D); After a 2-week run-in/wash-off period, participants received single daily doses of 120 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 20 mg Twice Daily (Panel E); After a 2-week run-in/wash-off period, participants received twice-daily doses (b.i.d.) of 120 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 30 mg Twice Daily (Panel F); After a 2-week run-in/wash-off period, participants received twice-daily doses of 30 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 50 mg Twice Daily (Panel G); After a 2-week run-in/wash-off period, participants received twice-daily doses of 50 mg MK-1006 over a 10-day multiple-dosing period while remaining domiciled in the CRU.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 120 mg Once Daily Outpatient (Panel H); After a 2-week run-in/wash-off period, participants received single daily doses of 120 mg MK-1006 over a 7-day multiple-dosing period while remaining domiciled in the CRU. Participants were then discharged from the CRU and continued daily dosing of MK-1006 for an additional 21 days as outpatients.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Experimental: MK-1006 50 mg Twice Daily Outpatient (Panel I); After a 2-week run-in/wash-off period, participants received twice-daily doses of 50 mg MK-1006 over a 7-day multiple-dosing period while remaining domiciled in the CRU. Participants were then discharged from the CRU and continued daily dosing of MK-1006 for an additional 21 days as outpatients.	Drug: MK-1006; MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Placebo Comparator: Placebo; After a 2-week run-in/wash-off period, participants received dose-matched placebo to MK-1006 over a multiple-dosing period while remaining domiciled in the CRU.	Drug: Comparator: Placebo comparator; Dose-matched MK-1006 placebo capsules (1 mg, 10 mg and 20 mg) administered orally over a multiple dosing period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Adverse Events (AEs) On Study	An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event.	From Day 1 through the end of poststudy period (up to Day 25)
Number of Participants Who Discontinued Treatment Due to an AE	An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event.	From Day 1 through the end of poststudy period (up to Day 25)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG)	Plasma glucose concentration was determined using a glucometer and measured before drug was given to establish a baseline fasting plasma glucose concentration. Plasma glucose concentrations were then measured every ~30 minutes over a 24 hour period after the Day 1 dose (First Dosing Day) and after the Day 10 dose (Last Dosing Day) to obtain a weighted mean average value for Day 1 and for Day 10. Results were expressed as the change from baseline to the Day 1 weighted average (First Dosing Day), and as the change from baseline to the Day 10 weighted average (Last Dosing Day).	Day -1 (pre-dose baseline), Day 1 (First Dosing Day), Day 10 (Last Dosing Day)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: September 23, 2008
• First Submitted That Met QC Criteria: September 23, 2008
• First Posted (Estimate): September 25, 2008

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 1006-004; 2008_550