Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8655 in Participants With Type 2 Diabetes (MK-8655-002)

Phase 1

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: MK-8655; Drug: Placebo

• Registration Number: NCT01640873
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This study will assess the initial safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-8655, after single and multiple daily oral administrations to participants with Type 2 Diabetes (T2DM). The study will assess the reduction in fasting plasma glucose concentrations from baseline after multiple daily administrations of MK-8655.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-12
• Study First Submitted QC: 2012-07-12
• Study First Posted: 2012-07-16
• Study Start: 2012-09-19
• Primary Completion: 2012-12-20
• Study Completion: 2012-12-20
• Status Verified: 2018-04
• Results First Submitted: 2018-04-25
• Results First Submitted QC: 2018-04-25
• Last Update Submitted: 2018-04-25
• Results First Posted: 2018-11-13
• Last Update Posted: 2018-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

• Male or female of non-child bearing potential
• Body Mass Index ≤40 kg/m^2
• Diagnosis of Type 2 Diabetes (T2DM) and is either drug naive or is being treated with metformin only
• In good health except for T2DM
• Willing to follow a standard diet
• Nonsmoker and/or no use of nicotine or nicotine-containing products for 6 months

Exclusion Criteria

• Mentally or legally incapacitated
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine (except T2DM), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of neoplastic or myeloproliferative diseases
• Has clinical unstable or rapidly progressing diabetic retinopathy, neuropathy, and/or frequent nausea, bloating or vomiting, severe gastroesophageal reflux or early satiety
• Has a history of Type 1 Diabetes and/or history of ketoacidosis
• Use of any lipid-lowering therapies in the past 3 months
• Non-permitted medication for a co-morbid condition
• Excessive alcohol or caffeine use
• Participation in another investigational study within 4 weeks prior to this study
• A history of significant multiple and/or severe allergies or anaphylactic reactions
• Regular user of any illicit drugs or history of alcohol abuse within 6 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MK-8655 80 mg/MK-8655 320 mg	MK-8655	Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Placebo	Placebo	Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.

Primary Outcome Measures

Name	Time	Method
Fasting Plasma Glucose (FPG)	Day 16 (Predose)	Blood for fasting plasma glucose (central laboratory) was obtained after at least 10 hours overnight fast.
Number of Participants With One or More Adverse Events	Up to 14 days after the last dose of study drug (Up to 31 days)	An adverse event 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 Discontinuing Study Drug Due to an Adverse Event	Up to 17 days	An adverse event 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

Name	Time	Method
True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24)	24 hours post dose on Days 1, 7, and 14	C24hr was log transformed and analyzed based on a linear mixed effects model containing fixed effects for treatment, day and treatment by day interaction and a random effect for the participant.
Change From Baseline at 2 Hours Oral Glucose Tolerance Test	Baseline and 2 hours after dosing on Days 1, 3, and 16	Plasma glucose excursion was assessed during an oral glucose tolerance test (oGTT) following a single dose administration of MK-8655 in participants with T2DM.
24-Hour Weighted Mean Glucose (WMG)	Day 15: Predose, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 18, 21, 23 hours post-dose.	The WMG provides an integrated assessment of the glycemic exposure over the 24-hour period. To reduce variability of the baseline (before any study drug administration) WMG, participants were domiciled in the test facility at least 36 hours prior to Day 1, where standard meals were provided, and physical activity was monitored. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The sample scheme for the 18 point glucose measurements used in this study had many samples taken in the very early morning hours, as well as the first three hours after meals. WMG was calculated as the area under the curve (AUC) of the glucose concentrations divided by the duration of time of samples collected.