Assessment of Pharmacokinetics of Single Dose Odanacatib (MK-0822) in Participants With Moderate Hepatic Insufficiency (MK-0822-070)

Single Dose Study to Investigate the Pharmacokinetics of Odanacatib (MK-0822) in Subjects With Hepatic Insufficiency

This open-label, non-randomized study was designed to compare pharmacokinetics of a single 50 milligram (mg) dose of MK-0822 in participants with and without moderate hepatic insufficiency (abnormal liver function) in order to determine to what degree hepatic dysfunction may impact therapeutic blood levels of MK-0822. The primary hypothesis is that plasma AUC0-∞ of odanacatib in participants with moderate hepatic insufficiency is similar to that in matched healthy participants following a single 50 mg oral dose.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: MK-0822

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Not currently pregnant, nursing or planning to be pregnant through-out the course of the study; agree to use specified contraception per protocol requirement
• Body Mass Index (BMI) of ≤ 39 kg/m^2 (not obese)
• Judged to be in good health (for healthy participant population)
• Non-smoker for the past 6-months; social smokers (smoke less than 10 cigarettes within the past 3 months; or per discretion of the study Investigator, quit smoking within the past 3 months.
• Diagnosed with chronic (more than 6 months), stable (no acute episodes of illness within the previous 2 months) hepatic insufficiency (liver dysfunction) with features of cirrhosis due to any cause (for the moderate hepatic insufficiency participant population)
• Possess the ability to understand the study, grant voluntary informed consent and willingly comply with all study requirements

Exclusion Criteria:

• Does not meet the age requirement, is mentally or legally incapacitated, has or is expected to have significant emotional problems, or a history of a clinically significant psychiatric disorder
• Has been diagnosed with a disease or medical condition which may pose a risk to the participant or may confound the study results
• Compromised renal (kidney) function, significant organ system disease(s) or cancer(s)
• Unable to refrain from or anticipates the use of any new medication, including prescription and non-prescription drugs or herbal remedies
• Meets the requirements of the study in regard to current medication profile including: prescribed medications, caffeine, alcohol, over-the-counter drugs, herbals and nutritional products; with expected non-use of recreational (illicit) drugs associated with misuse, abuse and/or addiction
• Had surgery, donated 1 unit of blood or received another investigational study medication within 4 weeks prior to the study's first dose of investigational product
• History of multiple and/or severe allergies, or has had a life-threatening reaction or inability to tolerate prescription or non-prescription drugs or food

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate Hepatic Insufficiency Group; Single-dose administration of odanacatib 50 mg to participants with moderate hepatic insufficiency.	Drug: MK-0822; A single oral dose (50 mg tablet) of MK 0822 will be administered on Day 1 after an overnight fast.; Other Names: odanacatib
Experimental: Healthy Matched Control Group; Single-dose administration of odanacatib 50 mg to healthy matched control participants.	Drug: MK-0822; A single oral dose (50 mg tablet) of MK 0822 will be administered on Day 1 after an overnight fast.; Other Names: odanacatib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose	For healthy and moderate hepatic insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of AUC0-∞ (Total AUC). AUC0-∞ is a measure of total drug exposure.	Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of MK-0822 After Single Dose	For healthy and moderate hepatic insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Cmax.	Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Time to Maximum Concentration (Tmax) of MK-0822 After Single Dose	For healthy and moderate hepatic insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Tmax.	Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Apparent Terminal Half-life (t1/2) of MK-0822 After Single Dose	Apparent terminal half-life is the time required to divide the plasma (serum) concentration by two after reaching pseudo-equilibrium. (Note: it is not the time required to eliminate half the administered dose.) For healthy and moderate hepatic insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of t1/2. Results are presented using harmonic mean and jackknife standard deviation.	Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2012
• Primary Completion (Actual): April 24, 2012
• Study Completion (Actual): April 24, 2012

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (Estimate): January 19, 2012

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: July 30, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: 0822-070

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No