Hepatitis C Virus
Conditions
Brief summary
The primary objective of the study is to evaluate the single-dose pharmacokinetics (PK) of velpatasvir (formerly GS-5816) in participants with severe renal impairment using matched healthy participants as a control group.
Interventions
DRUGVelpatasvir
Velpatasvir 100 mg (2 x 50 mg tablets) 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: * General good health with stable chronic kidney disease in Severe Renal Impairment Group * Screening labs within defined thresholds * Creatinine clearance must be \< 30 mL/min for Severe Renal Impairment group, and ≥ 90 mL/min for Normal Renal Function group Key
Exclusion criteria
* Females who are pregnant or nursing, or males who have a pregnant partner * Infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV * History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with participant treatment and/or adherence to the protocol Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast | Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1 | AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. |
| PK Parameter of Velpatasvir: AUCinf | Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1 | AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. |
| PK Parameter of Velpatasvir: Cmax | Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1 | Cmax is defined as the maximum observed plasma concentration of drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First dose date plus 30 days | Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug. |
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | First dose date plus 30 days | A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening). |
| Percentage Protein Binding of Velpatasvir | 2 or 3 hours post-dose on Day 1 | Mean velpatasvir protein binding (percentage free and percentage bound) was determined in all participants at 2 or 3 hours post-dose. Protein binding was assessed at Tmax whenever possible or at the time point closest to Tmax for each participant. |
Countries
New Zealand, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United Stated and New Zealand. The first participant was screened on 16 December 2013. The last study visit occurred on 09 June 2014.
Pre-assignment details
46 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1. | 9 |
| Severe Renal Impairment Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1. | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Severe Renal Impairment | Normal Renal Function | Total |
|---|---|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 4 | 66 years STANDARD_DEVIATION 3.7 | 68 years STANDARD_DEVIATION 4.7 |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 0 / 9 | 2 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.
Time frame: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1
Population: The PK analysis set included all enrolled and treated participants who have evaluable PK profiles for velpatasvir.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast | 5597.8 h*ng/mL | Standard Deviation 1749.18 |
| Severe Renal Impairment | Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast | 7971.7 h*ng/mL | Standard Deviation 2531.09 |
Comparison: A sample size of 8 evaluable participants in each renal function group (normal and severely impaired) will provide at least 80% power to reject the null hypothesis that participants with severe renal impairment have a minimum increase of 100% in AUC0-last, AUCinf, or Cmax of velpatasvir compared to participants with normal renal function.90% CI: [116.62, 190.49]
Primary
PK Parameter of Velpatasvir: AUCinf
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
Time frame: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | PK Parameter of Velpatasvir: AUCinf | 5651.6 h*ng/mL | Standard Deviation 1763.12 |
| Severe Renal Impairment | PK Parameter of Velpatasvir: AUCinf | 8108.3 h*ng/mL | Standard Deviation 2628.18 |
Comparison: A sample size of 8 evaluable participants in each renal function group (normal and severely impaired) will provide at least 80% power to reject the null hypothesis that participants with severe renal impairment have a minimum increase of 100% in AUC0-last, AUCinf, or Cmax of velpatasvir compared to participants with normal renal function.90% CI: [116.97, 192.11]
Primary
PK Parameter of Velpatasvir: Cmax
Cmax is defined as the maximum observed plasma concentration of drug.
Time frame: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | PK Parameter of Velpatasvir: Cmax | 702.7 ng/mL | Standard Deviation 197.2 |
| Severe Renal Impairment | PK Parameter of Velpatasvir: Cmax | 732.4 ng/mL | Standard Deviation 176.19 |
Comparison: A sample size of 8 evaluable participants in each renal function group (normal and severely impaired) will provide at least 80% power to reject the null hypothesis that participants with severe renal impairment have a minimum increase of 100% in AUC0-last, AUCinf, or Cmax of velpatasvir compared to participants with normal renal function.90% CI: [90.76, 135.38]
Secondary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.
Time frame: First dose date plus 30 days
Population: The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Renal Function | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 0 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 20 percentage of participants |
Secondary
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening).
Time frame: First dose date plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Renal Function | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 4 | 0 percentage of participants |
| Normal Renal Function | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 1 | 33.3 percentage of participants |
| Normal Renal Function | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 2 | 0 percentage of participants |
| Normal Renal Function | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 3 | 0 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 3 | 30 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 4 | 10 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 2 | 30 percentage of participants |
| Severe Renal Impairment | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 1 | 20 percentage of participants |
Secondary
Percentage Protein Binding of Velpatasvir
Mean velpatasvir protein binding (percentage free and percentage bound) was determined in all participants at 2 or 3 hours post-dose. Protein binding was assessed at Tmax whenever possible or at the time point closest to Tmax for each participant.
Time frame: 2 or 3 hours post-dose on Day 1
Population: Participants in the PK Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Percentage Protein Binding of Velpatasvir | Bound Protein Percentage | 99.71 percentage of plasma protein binding | Standard Deviation 0.012 |
| Normal Renal Function | Percentage Protein Binding of Velpatasvir | Free Protein Percentage | 0.29 percentage of plasma protein binding | Standard Deviation 0.012 |
| Severe Renal Impairment | Percentage Protein Binding of Velpatasvir | Free Protein Percentage | 0.29 percentage of plasma protein binding | Standard Deviation 0.012 |
| Severe Renal Impairment | Percentage Protein Binding of Velpatasvir | Bound Protein Percentage | 99.71 percentage of plasma protein binding | Standard Deviation 0.012 |