Hepatic Impairment
Conditions
Brief summary
The purpose of this study is to compare the pharmacokinetics (PK) of elpipodect 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 elpipodect in participants with mild hepatic impairment to healthy participants.
Interventions
DRUGElpipodect
Administered at a dose of 4 mg via oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189 | 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) | 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 | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 15 days | 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 | Up to approximately 15 days | 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. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
As prespecified in the protocol, the safety and pharmacokinetic (PK) data from Part 1 of the study, comparing participants with moderate hepatic impairment to healthy participants, were reviewed after completion of Part 1. Per protocol, a decision was made to not conduct Part 2 of the study, comparing participants with mild hepatic impairment to healthy participants.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hepatic Impairment Participants Participants with moderate hepatic impairment received a single dose of MK-8189 4 mg orally on Day 1. | 7 |
| Healthy Participants Healthy participants received a single dose of MK-8189 4 mg orally on Day 1. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Healthy Participants | Total | Moderate Hepatic Impairment Participants |
|---|---|---|---|
| Age, Continuous | 57.1 Years STANDARD_DEVIATION 8 | 56.4 Years STANDARD_DEVIATION 7.8 | 55.7 Years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 4 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
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.
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)
Population: All participants who were compliant with the study procedures and have available data from at least one treatment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Participants | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189 | 5600 h*nmol/L |
| Healthy Participants | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MK-8189 | 4710 h*nmol/L |
90% CI: [0.7, 2.01]
Primary
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.
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)
Population: All participants who were compliant with the study procedures and have available data from at least one treatment
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment Participants | Maximum Observed Plasma Concentration (Cmax) of MK-8189 | 194 nmol/L |
| Healthy Participants | Maximum Observed Plasma Concentration (Cmax) of MK-8189 | 158 nmol/L |
90% CI: [0.86, 1.74]
Secondary
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.
Time frame: Up to approximately 15 days
Population: All participants who received at least one dose of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hepatic Impairment Participants | Number of Participants Who Discontinue From the Study Due to an AE | 0 Participants |
| Healthy Participants | Number of Participants Who Discontinue From the Study Due to an AE | 0 Participants |
Secondary
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.
Time frame: Up to approximately 15 days
Population: All participants who received at least one dose of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hepatic Impairment Participants | Number of Participants Who Experience One or More Adverse Events (AEs) | 4 Participants |
| Healthy Participants | Number of Participants Who Experience One or More Adverse Events (AEs) | 0 Participants |