A Study to Assess Pharmacokinetics of Preladenant in Participants With Chronic Hepatic Impairment (P06513)

An Open-label, Single Dose, Oral Administration, Sequential Two Parts Study to Compare the Pharmacokinetics of SCH 420814 / MK-3814 in Subjects With Mild and Moderate Chronic Hepatic Impairment With Their Respectively Matching Healthy Volunteers

The purpose of this study is to compare the pharmacokinetics (PK) of preladenant after administration of a single 5 mg oral dose of preladenant in participants with hepatic impairment and healthy volunteers. Part 1 of this study compares healthy volunteers with participants with mild hepatic impairment. Part 2 compares healthy volunteers with participants with moderate hepatic impairment. Healthy volunteers in each part of this study are to be matched with participants with hepatic impairment by race, age, gender, and body mass index (BMI). The primary hypotheses are that in participants with mild or moderate HI, the area under the concentration-time curve from time 0 extrapolated to time of the last quantifiable concentration (AUC0-t) of preladenant is similar to that observed in matched healthy volunteers, so that the mean ratio of hepatic impaired/healthy is contained within the interval [0.50, 2.00].

Study Overview

• Status: Completed
• Conditions: Chronic Hepatic Impairment
• Intervention / Treatment: Drug: Preladenant

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria for Healthy Participants Groups:

• Must be healthy with normal hepatic function and be free of any clinically significant disease or condition that requires a physician's care and/or would interfere with study evaluations or procedures.

Key Inclusion Criteria for Hepatic Impaired Groups:

• Must have mild or moderate hepatic impairment.
• Must have a diagnosis of chronic liver disease for >6 months.
• Clinical laboratory tests, physical examination, and electrocardiographs must be clinically acceptable to the investigator and sponsor.
• Must be free, other than chronic liver disease, of significant medical conditions unrelated to their hepatic disorder except for conditions that in the opinion of the investigator may not interfere with the study evaluations, procedures or participation.

Key Exclusion Criteria

• Must not be on any prohibited medications for entry into the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Hepatic Impaired (HI) Part 1; Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.	Drug: Preladenant; After at least an 8 hours overnight fast, one 5-mg preladenant tablet, is administered orally, on Day 1.; Other Names: SCH 420814; MK-3814; Adenosine 2a Antagonist
Active Comparator: Healthy to Match Mild HI Part 1; Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.	Drug: Preladenant; After at least an 8 hours overnight fast, one 5-mg preladenant tablet, is administered orally, on Day 1.; Other Names: SCH 420814; MK-3814; Adenosine 2a Antagonist
Experimental: Moderate HI Part 2; Participants with moderate chronic liver disease enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.	Drug: Preladenant; After at least an 8 hours overnight fast, one 5-mg preladenant tablet, is administered orally, on Day 1.; Other Names: SCH 420814; MK-3814; Adenosine 2a Antagonist
Active Comparator: Healthy to Match Moderate HI Part 2; Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.	Drug: Preladenant; After at least an 8 hours overnight fast, one 5-mg preladenant tablet, is administered orally, on Day 1.; Other Names: SCH 420814; MK-3814; Adenosine 2a Antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUC 0-t) of Preladenant After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant.	Pre-dose up to 72 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Preladenant After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant.	Pre-dose up to 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC 0-t of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 434748.	Pre-dose up to 72 hours postdose
Cmax of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 434748.	Pre-dose up to 72 hours postdose
AUC 0-t of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 446637.	Pre-dose up to 72 hours postdose
Cmax of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 446637.	Pre-dose up to 72 hours postdose
AUC 0-t of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant calculated using free drug concentration.	Pre-dose up to 72 hours postdose
Cmax of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant	For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant calculated using free drug concentration.	Pre-dose up to 72 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2011
• Primary Completion (Actual): June 14, 2012
• Study Completion (Actual): June 14, 2012

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 1, 2011
• First Posted (Estimate): November 4, 2011

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Parkinson disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: P06513; MK-3814-034 (Other Identifier: Merck & Co.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf