Hepatitis C
Conditions
Brief summary
This study will compare the pharmacokinetics (PK) of grazoprevir (MK-5172) when administered to participants with mild, moderate or severe hepatic insufficiency (assessed by the criteria of the Child-Pugh's scale) with the PK of grazoprevir when administered to healthy participants.
Interventions
DRUGGrazoprevir
Part 1: oral morning dose of 200 mg daily for 10 days Part 2: oral morning dose of 100 mg daily for 10 days Part 3: oral morning dose of 50 mg daily 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 65 Years
Healthy volunteers
Yes
Inclusion criteria
* If female, must be of non-childbearing potential or willing to use at least 2 acceptable methods of contraception from enrollment to 2 weeks after the last dose of study drug * No clinically significant abnormality on electrocardiogram Hepatic Insufficiency Participants Only: * Other than hepatic insufficiency with features of cirrhosis, is otherwise in good health based on medical history, physical examination, vital signs, and laboratory safety tests * Chronic (\>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology * Score on the Child-Pugh scale must range from 5 to 6 (mild hepatic insufficiency) to from 7 to 9 (moderate hepatic insufficiency) to from 10 to 15 (severe hepatic insufficiency) Matched Healthy Participants Only: \- In good health based on medical history, physical examination, vital signs, and laboratory safety tests
Exclusion criteria
* History of any illness that might confound the results of the study or poses an additional risk to the participant * History of clinically significant endocrine, gastrointestinal (other than related to their hepatic impairment), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases * Pregnancy * Estimated creatinine clearance of ≤60 mL/min * History of stroke, chronic seizures, or major neurological disorder * History of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment * Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort, green tea, gingko, coenzyme Q, ginseng, echinacea, etc.) or nutritional supplements (e.g., garlic supplements), beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study, until the poststudy visit * Participated in another investigational study within 4 weeks * History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food Hepatic Insufficiency Participants Only: \- Has a history of hepatitis C infection by serology, regardless of most recent viral load status. Matched Healthy Participants Only: * History of any chronic and/or active hepatic disease including elevations of serum transaminases, hepatitis, biliary tract disease, or a history of any significant gastrointestinal surgery. * History of hepatitis C. Participants with a history of self-limited hepatitis A with complete resolution documented at least 6 months prior to entry will be eligible for inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Maximum Concentration (Cmax) of Grazoprevir | Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Time to Peak Concentration (Tmax) of Grazoprevir | Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI | Day 1 at 24 hours postdose | Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI | Day 1 at 24 hours postdose | Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | Days 10 at 24 hours postdose | Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
| Apparent Terminal Half-life (t1/2) of Grazoprevir | Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1-Mild HI Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. | 8 |
| Part 1-Healthy Matched to Mild HI Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. | 8 |
| Part 2-Moderate HI Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. | 9 |
| Part 2-Healthy Matched to Moderate HI Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. | 9 |
| Part 3-Severe HI Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. | 8 |
| Part 3-Healthy Matched to Severe HI Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. | 8 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Elective Surgery | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1-Mild HI | Part 1-Healthy Matched to Mild HI | Part 2-Moderate HI | Part 2-Healthy Matched to Moderate HI | Part 3-Severe HI | Part 3-Healthy Matched to Severe HI | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.1 Years STANDARD_DEVIATION 4.1 | 54.5 Years STANDARD_DEVIATION 5.8 | 53.3 Years STANDARD_DEVIATION 6.7 | 52.3 Years STANDARD_DEVIATION 6.8 | 52.1 Years STANDARD_DEVIATION 8.4 | 52.0 Years STANDARD_DEVIATION 9.9 | 53.1 Years STANDARD_DEVIATION 6.9 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 9 Participants | 9 Participants | 5 Participants | 5 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 5 / 8 | 4 / 9 | 4 / 9 | 4 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 9 | 1 / 8 | 0 / 8 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1-Mild HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 54.24 hr. | Geometric Coefficient of Variation 22.32 |
| Part 1-Healthy Matched to Mild HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 35.85 hr. | Geometric Coefficient of Variation 47.15 |
| Part 2-Moderate HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 39.59 hr. | Geometric Coefficient of Variation 23.76 |
| Part 2-Healthy Matched to Moderate HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 39.80 hr. | Geometric Coefficient of Variation 17.34 |
| Part 3-Severe HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 42.00 hr. | Geometric Coefficient of Variation 26.55 |
| Part 3-Healthy Matched to Severe HI | Apparent Terminal Half-life (t1/2) of Grazoprevir | 31.02 hr. | Geometric Coefficient of Variation 41.99 |
Primary
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1-Mild HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 1.71 uM*hr |
| Part 1-Mild HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 6.20 uM*hr |
| Part 1-Healthy Matched to Mild HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 1.42 uM*hr |
| Part 1-Healthy Matched to Mild HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 3.74 uM*hr |
| Part 2-Moderate HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 1.61 uM*hr |
| Part 2-Moderate HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 4.21 uM*hr |
| Part 2-Healthy Matched to Moderate HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 0.321 uM*hr |
| Part 2-Healthy Matched to Moderate HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 0.874 uM*hr |
| Part 3-Severe HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 1.17 uM*hr |
| Part 3-Severe HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 3.00 uM*hr |
| Part 3-Healthy Matched to Severe HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 1 | 0.0592 uM*hr |
| Part 3-Healthy Matched to Severe HI | Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir | Day 10 | 0.257 uM*hr |
Comparison: Day 190% CI: [0.73, 2.01]
Comparison: Day 1090% CI: [1.05, 2.61]
Comparison: Day 190% CI: [2.19, 11.56]
Comparison: Day 1090% CI: [2.6, 8.93]
Comparison: Day 190% CI: [8.11, 48.51]
Comparison: Day 1090% CI: [6.1, 22.35]
Primary
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10
Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Days 10 at 24 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1-Mild HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 32.6 nM |
| Part 1-Healthy Matched to Mild HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 17.0 nM |
| Part 2-Moderate HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 48.9 nM |
| Part 2-Healthy Matched to Moderate HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 13.6 nM |
| Part 3-Severe HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 55.0 nM |
| Part 3-Healthy Matched to Severe HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10 | 5.89 nM |
90% CI: [1.4, 2.63]
90% CI: [1.81, 7.11]
90% CI: [4.98, 17.51]
Primary
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Day 1 at 24 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants with Severe HI and Matched Healthy to Severe HI are absent because they had a different Measure Type and Method of Dispersion
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1-Mild HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI | 21.4 nM |
| Part 1-Healthy Matched to Mild HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI | 11.5 nM |
| Part 2-Moderate HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI | 17.7 nM |
| Part 2-Healthy Matched to Moderate HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI | 5.90 nM |
90% CI: [1.54, 2.24]
90% CI: [1.31, 6.82]
Primary
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Day 1 at 24 hours postdose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants with Mild HI, Moderate HI and Healthy Matched to Mild HI or Moderate HI are absent because they had a different Measure Type and Method of Dispersion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 3-Severe HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI | 15.6 nM |
| Part 3-Healthy Matched to Severe HI | Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI | 1.86 nM |
Primary
Maximum Concentration (Cmax) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1-Mild HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.257 uM |
| Part 1-Mild HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 1.40 uM |
| Part 1-Healthy Matched to Mild HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.305 uM |
| Part 1-Healthy Matched to Mild HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 1.02 uM |
| Part 2-Moderate HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.433 uM |
| Part 2-Moderate HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 0.631 uM |
| Part 2-Healthy Matched to Moderate HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.0580 uM |
| Part 2-Healthy Matched to Moderate HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 0.106 uM |
| Part 3-Severe HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.238 uM |
| Part 3-Severe HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 0.396 uM |
| Part 3-Healthy Matched to Severe HI | Maximum Concentration (Cmax) of Grazoprevir | Day 1 | 0.0157 uM |
| Part 3-Healthy Matched to Severe HI | Maximum Concentration (Cmax) of Grazoprevir | Day 10 | 0.0304 uM |
Comparison: Day 190% CI: [0.35, 2.01]
Comparison: Day 1090% CI: [0.83, 2.27]
Comparison: Day 190% CI: [2.74, 21.27]
Comparison: Day 1090% CI: [2.84, 12.57]
Comparison: Day 190% CI: [6.02, 38.25]
Comparison: Day 1090% CI: [6, 28.21]
Primary
Time to Peak Concentration (Tmax) of Grazoprevir
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Time frame: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1-Mild HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 3.50 hr. |
| Part 1-Mild HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 3.00 hr. |
| Part 1-Healthy Matched to Mild HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 2.50 hr. |
| Part 1-Healthy Matched to Mild HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 3.01 hr. |
| Part 2-Moderate HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 2.00 hr. |
| Part 2-Moderate HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 3.00 hr. |
| Part 2-Healthy Matched to Moderate HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 1.75 hr. |
| Part 2-Healthy Matched to Moderate HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 2.00 hr. |
| Part 3-Severe HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 1.75 hr. |
| Part 3-Severe HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 1.75 hr. |
| Part 3-Healthy Matched to Severe HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 1 | 1.50 hr. |
| Part 3-Healthy Matched to Severe HI | Time to Peak Concentration (Tmax) of Grazoprevir | Day 10 | 1.00 hr. |