A Pharmacokinetic Study of MK-3102 in Participants With Impaired Hepatic Function (MK-3102-031)

• ClinicalTrials.gov Identifier: NCT01767688
• Recruitment Status: Completed
• First Posted: January 14, 2013
• Results First Posted: October 29, 2015
• Last Update Posted: September 10, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

This study will investigate and compare the pharmacokinetics of a single 25-mg dose of MK-3102 in participants with moderate hepatic impairment and matched healthy participants. The primary hypothesis is that in participants with moderately impaired hepatic function, the area under the concentration-time curve from time zero to infinity (AUC0-∞) is similar to that observed in healthy matched control participants following a single 25 mg oral dose of MK-3102. Specifically, the true ratio (moderately impaired hepatic function patients/healthy matched control subjects) of geometric means for AUC0-∞ is no greater than 2.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: MK-3102	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Dose Study to Investigate the Pharmacokinetics of MK-3102 in Patients With Impaired Hepatic Function
• Actual Study Start Date: January 16, 2013
• Actual Primary Completion Date: March 1, 2013
• Actual Study Completion Date: March 7, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Moderate Hepatic Impairment Group	Drug: MK-3102; Single dose of 25 mg of MK-3102 (1 x 25 mg capsule) administered orally on Day 1.
Experimental: Healthy Matched Control Group	Drug: MK-3102; Single dose of 25 mg of MK-3102 (1 x 25 mg capsule) administered orally on Day 1.

Outcome Measures

Primary Outcome Measures :

1. Area Under the Plasma Concentration Versus Time Curve (AUC) From Hour 0 to Infinity (AUC0-∞) [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose ]

Secondary Outcome Measures :

1. Area Under the Concentration Versus Time Curve From Hour 0 to 168 Hours After Dosing (AUC0-168h) [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose ]
2. Plasma Concentration at 168 Hours After Dosing (C168h) [ Time Frame: 168 hours post-dose ]
3. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose ]
4. Time to Maximum Observed Plasma Drug Concentration (Tmax) [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose ]
5. Apparent Terminal Phase Half-life (t½) [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 96, and 168 hours post-dose ]
6. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 14 days post-dose ]
   An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
7. Number of Participants Discontinued From Study Due to AEs [ Time Frame: Up to 14 days post-dose ]
   An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation patient/subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Impaired Hepatic Function Participants:

• A diagnosis of:

  1. Chronic (> 6 months) hepatic insufficiency
  2. Stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology
• Score on the Child-Pugh Scale of 7 to 9 (moderate hepatic insufficiency)
• Estimated creatinine clearance (CLCr) > 60 mL/min or glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m^2

Both Impaired Hepatic Function and Healthy Participants:

• In general good health
• Continuous non-smokers or moderate smokers for at least 3 months prior to study start
• Body Mass Index ≤39 kg/m^2
• Females of reproductive potential must have a negative pregnancy test and agree to use acceptable birth control method(s) or remain sexually inactive throughout study
• Non-vasectomized male patients must agree to use acceptable birth control method(s) or abstain from sexual intercourse during the trial and for 3 months after the study

Exclusion Criteria:

Healthy Participants:

• History or presence of alcoholism within the past 2 years
• Presence of hepatitis B virus (HBV) or hepatitis virus C (HVC)

Both Impaired Hepatic Function and Healthy Participants:

• History or presence of drug abuse within the past 2 years
• History or presence of human immunodeficiency virus (HIV)
• History or presence of significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (other than hepatic impairment), endocrine, immunologic, dermatologic, or neurological disease
• Use of any medication or substance (including prescription or over the counter, health supplements, natural or herbal supplements) which cannot be

discontinued at least 14 days prior to the study start and throughout the study

• Has been on a special diet within 28 days prior to the study start
• Blood donation within 56 days or plasma donation within 7 days prior to study start
• Participation in another clinical trial within 28 days of study start
• Women who are pregnant or nursing

Contacts and Locations

No Contacts or Locations Provided

More Information

Study Data/Documents: CSR Synopsis 

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01767688
• Other Study ID Numbers: 3102-031
• First Posted: January 14, 2013
• Results First Posted: October 29, 2015
• Last Update Posted: September 10, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme Corp.:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases