Chronic Hepatitis C, Renal Impairment
Conditions
Brief summary
Grazoprevir (MK-5172) and Elbasvir (MK-8742) were studied as the principal components of combination oral therapy for hepatitis C virus (HCV). The study examined the pharmacokinetic (PK) profiles of Grazoprevir and Elbasvir following 10 days of dosing in participants with end stage renal disease (ESRD) on hemodialysis (HD) or participants with severe renal impairment. Both groups were compared to healthy matched controls.
Interventions
DRUGGrazoprevir
100 mg oral tablet administered once a day for 10 days
DRUGElbasvir
50 mg oral tablet administered once a day for 10 days
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 80 Years
Healthy volunteers
Yes
Inclusion criteria
All Participants * For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using an acceptable birth control method. Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to the first dose * Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse during the trial and for 90 days after stopping the study medication and agree not to donate sperm during this time period Participants with ESRD on HD * Maintained on a stable regimen of HD within 3 months prior to first dosing Participants with Severe Renal Impairment * Estimated glomerular filtration rate (eGFR) at screening is \< 30 mL/min/1.73m\^2 Healthy Controls * Participant is within ± 10 years of the mean age and within 10% of the mean body mass index of severe renal impairment participants * eGFR at screening is \>=80 mL/min/1.73m\^2
Exclusion criteria
All Participants * History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable * History or presence of alcoholism and drug abuse within the past 6 months * Female participants who are pregnant or lactating * Regular user of any medication (including over the counter) that would significantly alter GFR * Donation of blood or significant blood loss within 56 days prior to the first dose of study medication(s) * Plasma donation within 7 days prior to the first dose of study medication(s) * A renal transplant or nephrectomy Participants with ESRD or Severe Renal Impairment * Rapidly fluctuating renal function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Up to 24 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | 24 hours postdose | Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Maximum Plasma Concentration (Cmax) of Grazoprevir | Up to 120 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9 |
| Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Up to 120 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9 |
| Apparent Terminal Half-life (T1/2) of Grazoprevir | Up to 120 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 |
| Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Up to 24 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir | Up to 24 hours postdose | Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10 |
| Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Up to 24 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | 24 hours postdose | Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Maximum Plasma Concentration (Cmax) of Elbasvir | Up to 120 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9 |
| Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Up to 120 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9 |
| Apparent Terminal Half-life (T1/2) of Elbasvir | Up to 120 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 |
| Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Up to 24 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants) |
| Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir | Up to 24 hours postdose | Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10 |
Participant flow
Recruitment details
After enrollment of participants with End Stage Renal Disease and Severe Renal Impairment, healthy participants with matching mean age, body mass index, and gender were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Participants With End Stage Renal Disease on Hemodialysis Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. | 8 |
| Participants With Severe Renal Impairment Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. | 8 |
| Healthy Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Participants With End Stage Renal Disease on Hemodialysis | Participants With Severe Renal Impairment | Healthy Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 47.8 Years | 65.8 Years | 55.1 Years | 56.2 Years |
| Estimated Glomerular Filtration Rate | NA mL/min/1.73 m^2 | 18.0 mL/min/1.73 m^2 | 93.4 mL/min/1.73 m^2 | NA mL/min/1.73 m^2 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 4 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 3 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 9 | 29.9 Liters/hr |
| Participants With End Stage Renal Disease | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 10 | 26.2 Liters/hr |
| Participants With Severe Renal Impairment: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 9 | NA Liters/hr |
| Participants With Severe Renal Impairment: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 10 | 13.9 Liters/hr |
| Healthy Participants: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 9 | NA Liters/hr |
| Healthy Participants: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir | Day 10 | 25.9 Liters/hr |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [0.83, 0.92]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.88, 1.53]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.77, 1.34]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [0.4, 0.72]
Primary
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 9 | 135 Liters/hr |
| Participants With End Stage Renal Disease | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 10 | 138 Liters/hr |
| Participants With Severe Renal Impairment: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 9 | NA Liters/hr |
| Participants With Severe Renal Impairment: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 10 | 69.4 Liters/hr |
| Healthy Participants: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 9 | NA Liters/hr |
| Healthy Participants: Day 10 | Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir | Day 10 | 114 Liters/hr |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [0.92, 1.15]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.8, 1.73]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.82, 1.78]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [0.4, 0.92]
Primary
Apparent Terminal Half-life (T1/2) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With End Stage Renal Disease | Apparent Terminal Half-life (T1/2) of Elbasvir | 23.04 Hours | Geometric Coefficient of Variation 6.34 |
| Participants With Severe Renal Impairment: Day 10 | Apparent Terminal Half-life (T1/2) of Elbasvir | 28.97 Hours | Geometric Coefficient of Variation 18.26 |
| Healthy Participants: Day 10 | Apparent Terminal Half-life (T1/2) of Elbasvir | 25.02 Hours | Geometric Coefficient of Variation 19.08 |
Primary
Apparent Terminal Half-life (T1/2) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants With End Stage Renal Disease | Apparent Terminal Half-life (T1/2) of Grazoprevir | 28.38 Hours | Geometric Coefficient of Variation 20.88 |
| Participants With Severe Renal Impairment: Day 10 | Apparent Terminal Half-life (T1/2) of Grazoprevir | 36.30 Hours | Geometric Coefficient of Variation 30.53 |
| Healthy Participants: Day 10 | Apparent Terminal Half-life (T1/2) of Grazoprevir | 35.18 Hours | Geometric Coefficient of Variation 19.64 |
Primary
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With End Stage Renal Disease | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir | 857 Liters |
| Participants With Severe Renal Impairment: Day 10 | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir | 569 Liters |
| Healthy Participants: Day 10 | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir | 901 Liters |
90% CI: [0.7, 1.3]
90% CI: [0.45, 0.89]
Primary
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Participants With End Stage Renal Disease | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir | 5430 Liters |
| Participants With Severe Renal Impairment: Day 10 | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir | 3490 Liters |
| Healthy Participants: Day 10 | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir | 5760 Liters |
90% CI: [0.63, 1.42]
90% CI: [0.39, 0.94]
Primary
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 9 | 1.89 uM*hr |
| Participants With End Stage Renal Disease | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 10 | 2.16 uM*hr |
| Participants With Severe Renal Impairment: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 9 | NA uM*hr |
| Participants With Severe Renal Impairment: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 10 | 4.07 uM*hr |
| Healthy Participants: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 9 | NA uM*hr |
| Healthy Participants: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir | Day 10 | 2.19 uM*hr |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [1.08, 1.21]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.65, 1.14]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.75, 1.3]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [1.38, 2.51]
Primary
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: Up to 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 9 | 0.969 uM*hr |
| Participants With End Stage Renal Disease | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 10 | 0.944 uM*hr |
| Participants With Severe Renal Impairment: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 9 | NA uM*hr |
| Participants With Severe Renal Impairment: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 10 | 1.88 uM*hr |
| Healthy Participants: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 9 | NA uM*hr |
| Healthy Participants: Day 10 | Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir | Day 10 | 1.14 uM*hr |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [0.87, 1.09]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.58, 1.25]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.56, 1.22]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [1.09, 2.49]
Primary
Maximum Plasma Concentration (Cmax) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 9 | 0.137 uM |
| Participants With End Stage Renal Disease | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 10 | 0.154 uM |
| Participants With Severe Renal Impairment: Day 10 | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 9 | NA uM |
| Participants With Severe Renal Impairment: Day 10 | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 10 | 0.271 uM |
| Healthy Participants: Day 10 | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 9 | NA uM |
| Healthy Participants: Day 10 | Maximum Plasma Concentration (Cmax) of Elbasvir | Day 10 | 0.163 uM |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [1, 1.26]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.62, 1.13]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.7, 1.27]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [1.21, 2.28]
Primary
Maximum Plasma Concentration (Cmax) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 9 | 0.141 uM |
| Participants With End Stage Renal Disease | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 10 | 0.135 uM |
| Participants With Severe Renal Impairment: Day 10 | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 9 | NA uM |
| Participants With Severe Renal Impairment: Day 10 | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 10 | 0.255 uM |
| Healthy Participants: Day 10 | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 9 | NA uM |
| Healthy Participants: Day 10 | Maximum Plasma Concentration (Cmax) of Grazoprevir | Day 10 | 0.154 uM |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [0.75, 1.22]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.57, 1.48]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.54, 1.42]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [0.99, 2.77]
Primary
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 9 | 46.9 nM |
| Participants With End Stage Renal Disease | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 10 | 58.2 nM |
| Participants With Severe Renal Impairment: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 9 | NA nM |
| Participants With Severe Renal Impairment: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 10 | 126 nM |
| Healthy Participants: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 10 | 60.9 nM |
| Healthy Participants: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir | Day 9 | NA nM |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [1.17, 1.32]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.56, 1.06]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.69, 1.32]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [1.46, 2.93]
Primary
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Time frame: 24 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 9 | 11.4 nM |
| Participants With End Stage Renal Disease | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 10 | 11.3 nM |
| Participants With Severe Renal Impairment: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 9 | NA nM |
| Participants With Severe Renal Impairment: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 10 | 23.3 nM |
| Healthy Participants: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 9 | NA nM |
| Healthy Participants: Day 10 | Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir | Day 10 | 14.5 nM |
Comparison: ESRD Non-HD Day 9 versus ESRD HD Day 1090% CI: [0.81, 1.19]
Comparison: ESRD Non-HD Day 9 versus Healthy Participants Day 1090% CI: [0.54, 1.16]
Comparison: ESRD HD Day 10 versus Healthy Participants Day 1090% CI: [0.53, 1.14]
Comparison: SRI Participants Day 10 versus Healthy Participants Day 1090% CI: [1.06, 2.42]
Primary
Time of Maximum Plasma Concentration (Tmax) of Elbasvir
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 9 | 4.00 Hours |
| Participants With End Stage Renal Disease | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 10 | 5.00 Hours |
| Participants With Severe Renal Impairment: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 9 | NA Hours |
| Participants With Severe Renal Impairment: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 10 | 4.00 Hours |
| Healthy Participants: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 9 | NA Hours |
| Healthy Participants: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Elbasvir | Day 10 | 4.00 Hours |
Primary
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Time frame: Up to 120 hours postdose
Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With End Stage Renal Disease | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 9 | 2.00 Hours |
| Participants With End Stage Renal Disease | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 10 | 2.50 Hours |
| Participants With Severe Renal Impairment: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 9 | NA Hours |
| Participants With Severe Renal Impairment: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 10 | 3.00 Hours |
| Healthy Participants: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 9 | NA Hours |
| Healthy Participants: Day 10 | Time of Maximum Plasma Concentration (Tmax) of Grazoprevir | Day 10 | 2.50 Hours |