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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000342-30 | EudraCT Number |
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The primary objective of this study is to evaluate the pharmacokinetics (PK), safety, and tolerability of a single dose of voxilaprevir (formerly GS-9857) in participants with normal hepatic function, moderate hepatic impairment and severe hepatic impairment. Participants in the healthy control group will be matched to participants with impaired hepatic function by gender, age (± 10 years), and body mass index (± 15%).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Moderate Hepatic Impaired | Experimental | Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1. |
|
| Severe Hepatic Impaired | Experimental | Participants with severe hepatic impairment and matched healthy controls will receive a single dose of voxilaprevir on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Voxilaprevir | Drug | 100 mg tablet administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 post-dose |
| 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. | 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 |
| 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. | 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 |
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Key Inclusion Criteria:
All individuals:
For individuals with moderate hepatic impairment:
For individuals with severe hepatic impairment:
For individuals with normal hepatic function:
Key Exclusion Criteria:
All individuals:
For individuals with moderate or severe hepatic impairment:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States | ||
| Texas Liver Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Lawitz E, Marbury T, Kirby BJ, Au NT, Mathias A, Stamm LM, et al. The Effect of Renal or Hepatic Impairment on the Pharmacokinetics of GS-9857, A Pan-Genotypic HCV NS3/4A Protease Inhibitor [Abstract FRI-167]. J Hepatology 2016:S613-S4. |
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54 participants were screened. 33 participants were enrolled, 14 participants with normal hepatic function, 10 with Moderate Hepatic Impairment (MHI), and 9 with Severe Hepatic Impairment (SHI). Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups.
Participants were enrolled at study sites in United States, Germany, and New Zealand. The first participant was screened on 24 March 2015. The last study visit occurred on 04 March 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Hepatic Function | Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| FG001 | Moderate Hepatic Impairment (MHI) | Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| FG002 | Severe Hepatic Impairment (SHI) | Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety Analysis Set included all participants who took at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Hepatic Function | Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| BG001 | Moderate Hepatic Impairment (MHI) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups. | Posted | Geometric Mean | 95% Confidence Interval | h*ng/mL | 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 post-dose |
|
First dose date up to 31 days
Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normal Hepatic Function | Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C000619503 | voxilaprevir |
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| San Antonio |
| Texas |
| 78215 |
| United States |
| APEX GmbH | München | 81241 | Germany |
| Auckland Clinical Studies | Auckland | 1142 | New Zealand |
Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.
| BG002 | Severe Hepatic Impairment (SHI) | Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| OG001 | Severe Hepatic Impairment (SHI) | Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. |
| OG002 | Normal Hepatic Function (Matched Control for MHI) | Normal Hepatic Function (matched control for MHI) included participants that served as controls for participants with MHI. |
| OG003 | Normal Hepatic Function (Matched Controls for SHI) | Normal hepatic function (matched controls for SHI) included participants that served as controls for participants with SHI. |
|
|
|
| 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. | Participants in the PK Analysis Set were analyzed. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups. | Posted | Geometric Mean | 95% Confidence Interval | h*ng/mL | 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 |
|
|
|
|
| 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. | Participants in the PK Analysis Set were analyzed. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | 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 |
|
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 2 |
| 14 |
| EG001 | Moderate Hepatic Impairment (MHI) | Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG002 | Severe Hepatic Impairment (SHI) | Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1. | 0 | 9 | 0 | 9 | 1 | 9 |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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.
| GLSM Ratio (%) |
| 599.63 |
| 2-Sided |
| 90 |
| 342.36 |
| 1050.22 |
| Other |
An ANOVA appropriate was fitted to the natural logarithmic transformation of voxilaprevir Cmax. A 90% CI was constructed for the GLSM ratio of AUClast for the comparison groups using two 1-sided tests.
| GLSM Ratio (%) |
| 713.92 |
| 2-Sided |
| 90 |
| 384.07 |
| 1327.06 |
| Other |