search
Back to results

A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MK-8189
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Is a continuous non-smoker or moderate smoker (of fewer than 20 cigarettes/day or equivalent)
  • Female participant is not pregnant or breastfeeding and is not woman of childbearing potential (WOCBP) or is a WOCBP using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 14 days after the last dose of study intervention
  • (For hepatically impaired participants) Has a diagnosis of chronic (>6 months), stable (no acute episodes within the previous 2 months due to deterioration in hepatic function) hepatic impairment

Exclusion Criteria:

  • Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
  • Has a history of cancer; exceptions include (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, (2) other successfully treated malignancies
  • Has a history of significant multiple and/or severe allergies or has had significant intolerability to prescription or non-prescription drugs or food
  • Is positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
  • Has had major surgery or lost 1 unit of blood within 4 weeks prior to prestudy visit
  • Consumes greater than 3 glasses of alcoholic beverages per day
  • Consumes greater than 6 servings (1 serving is ~120 mg of caffeine) caffeinated beverages per day
  • (For hepatically impaired participants) Is taking medications to treat chronic medical conditions and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medications during study

Sites / Locations

  • ProSciento Inc. ( Site 0002)
  • Clinical Pharmacology of Miami ( Site 0001)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Moderate Hepatic Impairment Participants

Healthy Participants

Arm Description

Participants with hepatic impairment will receive a single dose of MK-8189 4 mg orally on Day 1.

Healthy participants will receive a single dose of MK-8189 4 mg orally on Day 1.

Outcomes

Primary Outcome Measures

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189
AUC0-inf is a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood samples collected pre and post-dose at multiple timepoints were used to estimate AUC0-inf following MK-8189 administration. Geometric least-squares mean and confidence intervals for AUC0-inf were calculated using a linear fixed effects model performed on natural log-transformed values.
Maximum Observed Plasma Concentration (Cmax) of MK-8189
Cmax is the maximum concentration of MK-8189 observed in plasma. Blood samples collected pre and post-dose at multiple timepoints were used to estimate Cmax following MK-8189 administration. Geometric least-squares mean and confidence intervals of Cmax were calculated using a linear fixed effects model performed on natural log-transformed values.

Secondary Outcome Measures

Number of Participants Who Experience One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be reported.
Number of Participants Who Discontinue From the Study Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study due to an AE will be reported.

Full Information

First Posted
December 15, 2020
Last Updated
December 5, 2022
Sponsor
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT04676425
Brief Title
A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)
Official Title
A 2-part, Open-label, Single-dose Study to Investigate the Influence of Hepatic Impairment on the Pharmacokinetics of MK-8189
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 17, 2021 (Actual)
Primary Completion Date
January 16, 2022 (Actual)
Study Completion Date
January 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to compare the pharmacokinetics (PK) of MK-8189 in participants with moderate hepatic impairment (based on the Child-Pugh classification) to healthy participants. This is Part 1 of the study; following review of the safety and PK data from Part 1, a decision will be made as to whether Part 2 of the study will be initiated. If done, Part 2 of the study will compare the PK of MK-8189 in participants with mild hepatic impairment to healthy participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Moderate Hepatic Impairment Participants
Arm Type
Experimental
Arm Description
Participants with hepatic impairment will receive a single dose of MK-8189 4 mg orally on Day 1.
Arm Title
Healthy Participants
Arm Type
Experimental
Arm Description
Healthy participants will receive a single dose of MK-8189 4 mg orally on Day 1.
Intervention Type
Drug
Intervention Name(s)
MK-8189
Intervention Description
Administered at a dose of 4 mg via oral tablet
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189
Description
AUC0-inf is a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood samples collected pre and post-dose at multiple timepoints were used to estimate AUC0-inf following MK-8189 administration. Geometric least-squares mean and confidence intervals for AUC0-inf were calculated using a linear fixed effects model performed on natural log-transformed values.
Time Frame
Pre-dose (0), 2, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose (hepatic impairment and healthy participants); 60, 84, 108 and 120 hours post-dose (hepatic impairment participants)
Title
Maximum Observed Plasma Concentration (Cmax) of MK-8189
Description
Cmax is the maximum concentration of MK-8189 observed in plasma. Blood samples collected pre and post-dose at multiple timepoints were used to estimate Cmax following MK-8189 administration. Geometric least-squares mean and confidence intervals of Cmax were calculated using a linear fixed effects model performed on natural log-transformed values.
Time Frame
Pre-dose (0), 2, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 96 hours post-dose (hepatic impairment and healthy); 60, 84, 108 and 120 hours post-dose (hepatic impairment)
Secondary Outcome Measure Information:
Title
Number of Participants Who Experience One or More Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be reported.
Time Frame
Up to approximately 15 days
Title
Number of Participants Who Discontinue From the Study Due to an AE
Description
An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study due to an AE will be reported.
Time Frame
Up to approximately 15 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Is a continuous non-smoker or moderate smoker (of fewer than 20 cigarettes/day or equivalent) Female participant is not pregnant or breastfeeding and is not woman of childbearing potential (WOCBP) or is a WOCBP using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 14 days after the last dose of study intervention (For hepatically impaired participants) Has a diagnosis of chronic (>6 months), stable (no acute episodes within the previous 2 months due to deterioration in hepatic function) hepatic impairment Exclusion Criteria: Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases Has a history of cancer; exceptions include (1) adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, (2) other successfully treated malignancies Has a history of significant multiple and/or severe allergies or has had significant intolerability to prescription or non-prescription drugs or food Is positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) Has had major surgery or lost 1 unit of blood within 4 weeks prior to prestudy visit Consumes greater than 3 glasses of alcoholic beverages per day Consumes greater than 6 servings (1 serving is ~120 mg of caffeine) caffeinated beverages per day (For hepatically impaired participants) Is taking medications to treat chronic medical conditions and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medications during study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
ProSciento Inc. ( Site 0002)
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Clinical Pharmacology of Miami ( Site 0001)
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

A Study to Investigate the Influence of Hepatic Impairment on MK-8189 Treatment (MK-8189-012)

We'll reach out to this number within 24 hrs