Renal Impairment
Conditions
Brief summary
This purpose of this study is to evaluate the plasma pharmacokinetics (PK) of N-hydroxycytidine (NHC), the nucleoside metabolite of molnupiravir, after a single oral dose of 800 mg molnupiravir in participants with severe renal impairment compared to healthy mean matched control participants. This study will also assess the safety and tolerability of molnupiravir in participants with severe renal impairment and the urinary excretion of NHC after a single oral dose of 800 mg molnupiravir in participants with severe renal impairment compared to healthy mean matched control participants. The primary hypothesis is that the plasma PK participants with severe renal impairment will be similar to that observed in the healthy mean matched control participants.
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 Criteria include but are not limited to the following: * Body mass index (BMI) ≥18.5 kg/m\^2 and ≤35 kg/m\^2 * Healthy participants: Baseline estimated glomerular filtration rate (eGFR) ≥90 mL/min based on the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation * Severe renal impairment participants: Baseline estimated glomerular filtration rate (eGFR) \<30 mL/min based on the 2021 CKD-EPI Creatinine equation
Exclusion criteria
The key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC) | Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose | Blood for plasma samples was collected at pre-specified time points to determine the AUC0-inf of NHC. |
| Maximum Plasma Concentration (Cmax) of NHC | Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose | Blood for plasma samples was collected at pre-specified time points to determine the Cmax of NHC. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to Day 15 | An AE was 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. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC) | Predose, 4, 8, 12 and 24 hours postdose | Urine was collected at pre-specified time points to determine the amount of dose Administered excreted in urine (Ae) of NHC. |
| Fraction of the Dose Administered Excreted in Urine (Fe) of NHC | Predose, 4, 8, 12 and 24 hours postdose | Urine was collected at pre-specified time points to determine the Fraction of the dose administered excreted in urine (Fe) of NHC. |
| Renal Clearance (CLr) of NHC | Predose, 4, 8, 12 and 24 hours postdose | Urine will be collected at pre-specified time points to determine the Renal Clearance (CLr) of NHC |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Severe Renal Impairment Participants with severe renal impairment received a single oral 800 mg dose of molnupiravir. | 8 |
| Healthy Participants With Normal Renal Function Participants in the healthy mean matched control group received a single oral 800 mg dose of molnupiravir. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Healthy Participants With Normal Renal Function | Total | Participants With Severe Renal Impairment |
|---|---|---|---|
| Age, Continuous | 59.6 Years STANDARD_DEVIATION 2 | 61.6 Years STANDARD_DEVIATION 5.9 | 63.5 Years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 4 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 | 3 Participants | 5 Participants | 2 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 | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC)
Blood for plasma samples was collected at pre-specified time points to determine the AUC0-inf of NHC.
Time frame: Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Severe Renal Impairment | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC) | 11100 hr*ng/mL |
| Healthy Participants With Normal Renal Function | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of N-hydroxycytidine (NHC) | 8960 hr*ng/mL |
90% CI: [0.94, 1.64]
Primary
Maximum Plasma Concentration (Cmax) of NHC
Blood for plasma samples was collected at pre-specified time points to determine the Cmax of NHC.
Time frame: Predose, 0.5,1.5, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With Severe Renal Impairment | Maximum Plasma Concentration (Cmax) of NHC | 3920 ng/mL |
| Healthy Participants With Normal Renal Function | Maximum Plasma Concentration (Cmax) of NHC | 3240 ng/mL |
90% CI: [0.9, 1.62]
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was 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. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported.
Time frame: Up to Day 15
Population: All participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Severe Renal Impairment | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Healthy Participants With Normal Renal Function | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
Secondary
Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC)
Urine was collected at pre-specified time points to determine the amount of dose Administered excreted in urine (Ae) of NHC.
Time frame: Predose, 4, 8, 12 and 24 hours postdose
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Severe Renal Impairment | Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC) | 3.72 mg | Geometric Coefficient of Variation 50.9 |
| Healthy Participants With Normal Renal Function | Amount of Dose Administered Excreted in Urine (Ae) of N-hydroxycytidine (NHC) | 14.6 mg | Geometric Coefficient of Variation 172 |
Secondary
Fraction of the Dose Administered Excreted in Urine (Fe) of NHC
Urine was collected at pre-specified time points to determine the Fraction of the dose administered excreted in urine (Fe) of NHC.
Time frame: Predose, 4, 8, 12 and 24 hours postdose
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Severe Renal Impairment | Fraction of the Dose Administered Excreted in Urine (Fe) of NHC | 0.591 % of administered dose | Geometric Coefficient of Variation 50.9 |
| Healthy Participants With Normal Renal Function | Fraction of the Dose Administered Excreted in Urine (Fe) of NHC | 2.33 % of administered dose | Geometric Coefficient of Variation 172 |
Secondary
Renal Clearance (CLr) of NHC
Urine will be collected at pre-specified time points to determine the Renal Clearance (CLr) of NHC
Time frame: Predose, 4, 8, 12 and 24 hours postdose
Population: All participants who complied with the protocol sufficiently to ensure that generated data likely exhibiting the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With Severe Renal Impairment | Renal Clearance (CLr) of NHC | 0.338 L/hr | Geometric Coefficient of Variation 62.1 |
| Healthy Participants With Normal Renal Function | Renal Clearance (CLr) of NHC | 1.64 L/hr | Geometric Coefficient of Variation 162 |