Trial Outcomes & Findings for Pharmacokinetics of Voxilaprevir in Adults With Normal Hepatic Function and Moderate or Severe Hepatic Impairment (NCT NCT02397707)

Last Updated: 2020-04-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

33 participants

Primary outcome timeframe

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

Results posted on

2020-04-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Normal Hepatic Function Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Moderate Hepatic Impairment (MHI) Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.
Overall Study STARTED	14	10	9
Overall Study COMPLETED	14	10	9
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Voxilaprevir in Adults With Normal Hepatic Function and Moderate or Severe Hepatic Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Hepatic Function n=14 Participants Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Moderate Hepatic Impairment (MHI) n=10 Participants Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) n=9 Participants Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Total n=33 Participants Total of all reporting groups
Age, Continuous	53 years STANDARD_DEVIATION 9.8 • n=5 Participants	55 years STANDARD_DEVIATION 6.7 • n=7 Participants	55 years STANDARD_DEVIATION 7.0 • n=5 Participants	54 years STANDARD_DEVIATION 8.0 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized Not Permitted	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	7 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment United States	11 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Region of Enrollment New Zealand	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Body Mass Index (BMI)	27.6 kg/m^2 STANDARD_DEVIATION 2.21 • n=5 Participants	27.6 kg/m^2 STANDARD_DEVIATION 3.90 • n=7 Participants	28.4 kg/m^2 STANDARD_DEVIATION 3.86 • n=5 Participants	27.8 kg/m^2 STANDARD_DEVIATION 3.18 • n=4 Participants

PRIMARY outcome

Timeframe: 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

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. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (MHI) n=10 Participants Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) n=9 Participants Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Normal Hepatic Function (Matched Control for MHI) n=10 Participants Normal Hepatic Function (matched control for MHI) included participants that served as controls for participants with MHI.	Normal Hepatic Function (Matched Controls for SHI) n=9 Participants Normal hepatic function (matched controls for SHI) included participants that served as controls for participants with SHI.
Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast	2058.5 h*ng/mL Interval 1034.0 to 4098.1	3872.5 h*ng/mL Interval 2173.1 to 6901.2	500.1 h*ng/mL Interval 307.0 to 814.6	601.2 h*ng/mL Interval 372.8 to 969.6

PRIMARY outcome

Timeframe: 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. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups.

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.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (MHI) n=10 Participants Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) n=9 Participants Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Normal Hepatic Function (Matched Control for MHI) n=10 Participants Normal Hepatic Function (matched control for MHI) included participants that served as controls for participants with MHI.	Normal Hepatic Function (Matched Controls for SHI) n=9 Participants Normal hepatic function (matched controls for SHI) included participants that served as controls for participants with SHI.
PK Parameter of Voxilaprevir: AUCinf	2227.1 h*ng/mL Interval 1122.0 to 4420.7	4107.5 h*ng/mL Interval 2331.7 to 7235.7	557.8 h*ng/mL Interval 351.8 to 884.6	685 h*ng/mL Interval 426.1 to 1101.2

PRIMARY outcome

Timeframe: 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. Five of the same participants with normal hepatic function served as matched controls for the MHI and SHI Arms/Groups.

Cmax is defined as the maximum observed plasma concentration of drug.Data presented are unadjusted geometric means and confidence intervals.

Outcome measures

Outcome measures
Measure	Moderate Hepatic Impairment (MHI) n=10 Participants Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) n=9 Participants Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Normal Hepatic Function (Matched Control for MHI) n=10 Participants Normal Hepatic Function (matched control for MHI) included participants that served as controls for participants with MHI.	Normal Hepatic Function (Matched Controls for SHI) n=9 Participants Normal hepatic function (matched controls for SHI) included participants that served as controls for participants with SHI.
PK Parameter of Voxilaprevir: Cmax	189.7 ng/mL Interval 85.2 to 422.3	370.8 ng/mL Interval 183.6 to 749.0	56.1 ng/mL Interval 38.2 to 82.2	51.9 ng/mL Interval 35.1 to 76.9

Adverse Events

Normal Hepatic Function

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Moderate Hepatic Impairment (MHI)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Severe Hepatic Impairment (SHI)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Normal Hepatic Function n=14 participants at risk Participants with normal hepatic function received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Moderate Hepatic Impairment (MHI) n=10 participants at risk Participants with moderate hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.	Severe Hepatic Impairment (SHI) n=9 participants at risk Participants with severe hepatic impairment received single dose of voxilaprevir 100 mg tablet orally on Day 1.
Gastrointestinal disorders Abdominal pain	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	10.0% 1/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	10.0% 1/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	10.0% 1/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	11.1% 1/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Headache	7.1% 1/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Neuropathy peripheral	0.00% 0/14 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	10.0% 1/10 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/9 • First dose date up to 31 days Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER