Pharmacokinetic Assessment of Single-Dose Odanacatib (MK-0822) in Subjects With Severe Renal Insufficiency (MK-0822-067)

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

This study will investigate and compare pharmacokinetics of a single 50 mg dose of odanacatib administered to participants with impaired renal/kidney function to those of a healthy matched control group. The primary hypothesis is that plasma AUC0-∞ of odanacatib in participants with impaired renal function is similar to that in matched healthy participants following a single 50 mg oral dose.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Not currently pregnant, nursing or planning to be pregnant through-out the course of the study; individual agrees to use specified contraception per protocol requirement for duration of study. Note: All females must have a serum pregnancy test to ensure and document negative test results prior to inclusion in the study.
• Body Mass Index (BMI) of up to 39.49kg/m^2
• Assessed to be in good health, including no clinically significant cardiac abnormalities based on results from an electrocardiogram (ECG) performed at pre-screening and/or prior to administration of study drug.
• 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.
• Agrees to adhere to all smoking and dietary restrictions associated with the study.
• Possess the ability to understand the study, grant voluntary informed consent, and willingly comply with all study requirements.

Inclusion Criterion Specific to Participants with Renal/Kidney Insufficiency:

• Creatinine clearance of <30 mL/min

Inclusion Criterion Specific to Healthy Volunteers:

• Creatine clearance of ≥ 90 mL/min (for healthy volunteers)

Exclusion Criteria:

• Does not meet the age requirement, is mentally or legally incapacitated, has or is expected to have significant emotional problems, and/or a history of a clinically significant psychiatric disorder.
• Diagnosed with a disease or medical condition which may pose a risk to the participant or may confound the study results.
• Has demonstrated or suspected stenosis (narrowing) of the renal artery, and/or has had a renal transplant and/or kidney removal.
• Has current, unstable, significant organ system disease(s) and/or cancer(s).
• Has had a surgical procedure, donated 1 unit of blood or received another investigational study medication within 4 weeks prior to the study's first dose of investigational product.
• Unable to refrain from or anticipates the use of any new medication, including prescription and non-prescription drugs and/or herbal remedies. Exceptions may include medications prescribed for prevention of disease or preservation of a healthy life.
• Uses any medication or agent that has the potential to significantly alter renal/kidney function.
• Unable to avoid taking diuretics (within 4 hours prior to and after dosing with the investigational product) or phosphate binders containing aluminum, calcium or lanthanum salts; iron supplements or other metal cations; antacids; or multivitamins containing iron or zinc (within 8 hours prior to dosing and 4 hours after dosing with the investigational product). Note: individuals prescribed to diuretics must be on a stable dose for at least 4 weeks prior to the study's start date in order to participate.
• History of multiple and/or severe allergies, has had a life-threatening reaction to a drug or other agent, and/or inability to tolerate prescription or nonprescription drugs and/or food.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Severe Renal Insufficiency Group; Single-dose administration of odanacatib 50 mg to participants with severe renal 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 severe renal 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 severe renal 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 severe renal 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	For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of t1/2.	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): January 17, 2012
• Primary Completion (ACTUAL): August 22, 2012
• Study Completion (ACTUAL): August 22, 2012

Study Registration Dates

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

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 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: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 0822-067

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