Hepatic Impairment
Conditions
Brief summary
The purpose of this study is to evaluate the pharmacokinetics (PK) of N-hydroxycytidine (NHC) following a single oral dose of molnupiravir in participants 18 to 75 years (inclusive) with moderate hepatic impairment and healthy matched controls.
Interventions
DRUGMolnupiravir
Four 200 mg capsules administered orally as a single dose
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
The key inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has a BMI ≥18.5 and ≤35 kg/m2 * Diagnosis of chronic (\>6 months) stable Hepatic Impairment (HI) with features of cirrhosis due to any etiology (Moderate HI arm only) * Has a score on the Child-Pugh scale ranging from 7 to 9 (Moderate HI arm only) * In good health (except for Moderate HI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) of Plasma N-Hydroxycitidine (NHC) | Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose | The plasma AUC0-∞ of NHC is reported. |
| Maximum Plasma Concentration (Cmax) of NHC | Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose | The plasma Cmax of NHC is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing ≥1 Adverse Event (AE) | Up to ~ 14 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
Countries
United States
Participant flow
Pre-assignment details
This study was conducted at 3 sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hepatic Impairment Participants with moderate hepatic impairment will receive a single oral 800mg dose of molnupiravir. | 7 |
| Healthy-Matched Control Group Healthy matched participants will receive a single oral 800mg dose of molnupiravir. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Healthy-Matched Control Group | Total | Moderate Hepatic Impairment |
|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 2.9 | 54.3 years STANDARD_DEVIATION 7.2 | 54.0 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 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 | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 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 | 0 / 7 | 1 / 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-∞) of Plasma N-Hydroxycitidine (NHC)
The plasma AUC0-∞ of NHC is reported.
Time frame: Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose
Population: All participants are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) of Plasma N-Hydroxycitidine (NHC) | 8930 hr*ng/mL |
| Healthy-Matched Control Group | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) of Plasma N-Hydroxycitidine (NHC) | 10900 hr*ng/mL |
Primary
Maximum Plasma Concentration (Cmax) of NHC
The plasma Cmax of NHC is reported.
Time frame: Day 1: Predose and 0.5, 1.5, 2, 4, 6, 8, 12, 24, 48, and 72 hours postdose
Population: All participants are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) of NHC | 3660 ng/mL |
| Healthy-Matched Control Group | Maximum Plasma Concentration (Cmax) of NHC | 3790 ng/mL |
Secondary
Number of Participants Experiencing ≥1 Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to ~ 14 days
Population: All participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Moderate Hepatic Impairment | Number of Participants Experiencing ≥1 Adverse Event (AE) | 0 Participants |
| Healthy-Matched Control Group | Number of Participants Experiencing ≥1 Adverse Event (AE) | 1 Participants |