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

Type 2 Diabetes Clinical Trial

Official title:

A Randomized Double-Blind Placebo-Controlled Single and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8655 in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01640873
• Other study ID #: 8655-002
• Secondary ID: MK-8655-002
• Status: Completed
• Phase: Phase 1
• Start date: September 19, 2012
• Est. completion date: December 20, 2012

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 20, 2012
• Est. primary completion date: December 20, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• MK-8655
Participants will receive MK-8655 as a single dose on Day 1. Participants will receive MK-8655, once a day (q.d.), for 14 consecutive days (Day 3 through Day 16). MK-8655 doses may be adjusted downward based on the results of ongoing studies.
• Placebo
Participants will receive Placebo as a single dose on Day 1. Participants will receive Placebo, q.d., for 14 consecutive days (Day 3 through Day 16).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With One or More Adverse Events	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.	Up to 14 days after the last dose of study drug (Up to 31 days)
Primary	Number of Participants Discontinuing Study Drug Due to an Adverse Event	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.	Up to 17 days
Primary	Fasting Plasma Glucose (FPG)	Blood for fasting plasma glucose (central laboratory) was obtained after at least 10 hours overnight fast.	Day 16 (Predose)
Secondary	True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24)	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.	24 hours post dose on Days 1, 7, and 14
Secondary	24-Hour Weighted Mean Glucose (WMG)	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.	Day 15: Predose, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 18, 21, 23 hours post-dose.
Secondary	Change From Baseline at 2 Hours Oral Glucose Tolerance Test	Plasma glucose excursion was assessed during an oral glucose tolerance test (oGTT) following a single dose administration of MK-8655 in participants with T2DM.	Baseline and 2 hours after dosing on Days 1, 3, and 16