NCT02397707

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

Completed Phase 1 Results posted Last updated 9 April 2020

What this trial tests

Phase 1 trial testing Voxilaprevir in HCV Infection in 33 participants. Completed in 4 March 2016.

Timeline

24 March 2015

Primary endpoint
4 March 2016

4 March 2016

Quick facts

Lead sponsor	Gilead Sciences
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	33
Start date	24 March 2015
Primary completion	4 March 2016
Estimated completion	4 March 2016
Sites	4 locations across New Zealand, United States, Germany

Drugs / interventions tested

• Voxilaprevir — full drug profile →

Conditions studied

• HCV Infection — all drugs for HCV Infection →

Sponsor

Gilead Sciences — full company profile →

Who can join

Adults 18 to 70, any sex, with HCV Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetic (PK) Parameter of Voxilaprevir: AUClast Primary · 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

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.

Group	Value	95% CI
Moderate Hepatic Impairment (MHI)	2058.5	1034 – 4098.1
Severe Hepatic Impairment (SHI)	3872.5	2173.1 – 6901.2
Normal Hepatic Function (Matched Control for MHI)	500.1	307 – 814.6
Normal Hepatic Function (Matched Controls for SHI)	601.2	372.8 – 969.6

PK Parameter of Voxilaprevir: AUCinf Primary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment (MHI)	2227.1	1122 – 4420.7
Severe Hepatic Impairment (SHI)	4107.5	2331.7 – 7235.7
Normal Hepatic Function (Matched Control for MHI)	557.8	351.8 – 884.6
Normal Hepatic Function (Matched Controls for SHI)	685	426.1 – 1101.2

PK Parameter of Voxilaprevir: Cmax Primary · 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.

Group	Value	95% CI
Moderate Hepatic Impairment (MHI)	189.7	85.2 – 422.3
Severe Hepatic Impairment (SHI)	370.8	183.6 – 749
Normal Hepatic Function (Matched Control for MHI)	56.1	38.2 – 82.2
Normal Hepatic Function (Matched Controls for SHI)	51.9	35.1 – 76.9

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose date up to 31 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Normal Hepatic Function

Serious: 0/14 (0%)

Deaths: 0/14

Moderate Hepatic Impairment (MHI)

Serious: 0/10 (0%)

Deaths: 0/10

Severe Hepatic Impairment (SHI)

Serious: 0/9 (0%)

Deaths: 0/9

Other adverse events (7 terms — click to expand)

Reaction	System	Normal Hepatic Function	Moderate Hepatic Impairmen…	Severe Hepatic Impairment …
Abdominal pain	Gastrointestinal disorders	—	—	—
Haemorrhoidal haemorrhage	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—

Data from ClinicalTrials.gov NCT02397707 adverse events section.

Sponsor's own description

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%).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections.
   Meshram RJ, Kathwate GH, Gacche RN. · · 2022 · cited 9× · PMID 35089390 · DOI 10.1007/s00705-022-05375-0