HCV Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the pharmacokinetics, safety, and tolerability of voxilaprevir (formerly GS-9857) in participants with severe renal impairment and matched healthy control participants.
Interventions
DRUGVoxilaprevir
100 mg tablet administered orally
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * All individuals: * Screening laboratory values within defined thresholds for group * Use of two effective contraception methods if female of childbearing potential or sexually active male * For individuals with severe renal impairment: * Stable chronic kidney disease * Creatinine clearance (CLcr) \< 30 mL/min Key
Exclusion criteria
* All individuals: * Pregnant or nursing female or male with pregnant female partner * Hepatitis B virus, hepatitis C virus (HCV) or HIV infection * History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol * For individuals with severe renal impairment: * Anticipated to require dialysis within 90 days of study dosing Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast | 0 (predose ≤ 5 min) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose | AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data presented are unadjusted geometric means and confidence intervals. |
| PK Parameter of Voxilaprevir: AUCinf | 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose | AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data presented are unadjusted geometric means and confidence intervals. |
| PK Parameter of Voxilaprevir: Cmax | 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose | Cmax is defined as the maximum observed plasma concentration of drug. Data presented are unadjusted geometric means and confidence intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities | First dose date to Day 31 | The percentage of participants experiencing any TEAE or treatment-emergent laboratory abnormality was summarized. |
Countries
Germany, New Zealand, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Germany, and New Zealand. The first participant was screened on 05 May 2015. The last study visit occurred on 28 September 2015.
Pre-assignment details
39 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Severe Renal Impairment Participants with severe renal impairment received a single dose of voxilaprevir 100 mg tablet orally on Day 1. | 10 |
| Normal Renal Function Participants with matched normal renal function received a single dose voxilaprevir of 100 mg tablet orally on Day 1. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Severe Renal Impairment | Total | Normal Renal Function |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 16 | 57 years STANDARD_DEVIATION 14.8 | 55 years STANDARD_DEVIATION 14.1 |
| Body Mass Index (BMI) | 26.2 kg/m^2 STANDARD_DEVIATION 5.54 | 26.4 kg/m^2 STANDARD_DEVIATION 4.74 | 26.6 kg/m^2 STANDARD_DEVIATION 4.08 |
| Creatinine Clearance | 21.2 mL/min STANDARD_DEVIATION 5.75 | 68.0 mL/min STANDARD_DEVIATION 49.34 | 114.8 mL/min STANDARD_DEVIATION 15.31 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Permitted | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment Germany | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment New Zealand | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 16 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 2 / 10 | 5 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data presented are unadjusted geometric means and confidence intervals.
Time frame: 0 (predose ≤ 5 min) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
Population: PK Analysis Set included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by the PK laboratory for the corresponding analyte.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Severe Renal Impairment | Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast | 662.7 h*ng/mL |
| Normal Renal Function | Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast | 383.3 h*ng/mL |
Comparison: An analysis of variance (ANOVA) appropriate for a parallel design was fitted to the natural logarithmic transformation of voxilaprevir AUClast. A 90% confidence interval (CI) was constructed for the geometric least squares mean (GLSM) ratio of AUClast for the comparison groups using two 1-sided tests.90% CI: [97.93, 305.33]
Primary
PK Parameter of Voxilaprevir: AUCinf
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data presented are unadjusted geometric means and confidence intervals.
Time frame: 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Severe Renal Impairment | PK Parameter of Voxilaprevir: AUCinf | 772.1 h*ng/mL |
| Normal Renal Function | PK Parameter of Voxilaprevir: AUCinf | 450.8 h*ng/mL |
Comparison: An ANOVA appropriate for parallel design was fitted to the natural logarithmic transformation of voxilaprevir AUCinf. A 90% CI was constructed for the GLSM ratio of AUCinf for the comparison groups using two 1-sided tests.90% CI: [97.65, 300.38]
Primary
PK Parameter of Voxilaprevir: Cmax
Cmax is defined as the maximum observed plasma concentration of drug. Data presented are unadjusted geometric means and confidence intervals.
Time frame: 0 (pre-dose ≤ 5 minutes), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 96, and 120 hours postdose
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Severe Renal Impairment | PK Parameter of Voxilaprevir: Cmax | 49.2 ng/mL |
| Normal Renal Function | PK Parameter of Voxilaprevir: Cmax | 33.9 ng/mL |
Comparison: An ANOVA appropriate for parallel design was fitted to the natural logarithmic transformation of voxilaprevir Cmax. A 90% CI was constructed for the GLSM ratio of Cmax for the comparison groups using two 1-sided tests.90% CI: [83.77, 252.48]
Secondary
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities
The percentage of participants experiencing any TEAE or treatment-emergent laboratory abnormality was summarized.
Time frame: First dose date to Day 31
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Severe Renal Impairment | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities | Any treatment-emergent laboratory abnormality | 70 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities | Any TEAE | 20 percentage of participants |
| Normal Renal Function | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities | Any TEAE | 50 percentage of participants |
| Normal Renal Function | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAE) and Laboratory Abnormalities | Any treatment-emergent laboratory abnormality | 30 percentage of participants |