Evidence map›Paper›PMID 29520729›Full record

Trial reportClinical pharmacokinetics2018

Pharmacokinetics and Safety of Velpatasvir and Sofosbuvir/Velpatasvir in Subjects with Hepatic Impairment.

Erik Mogalian, Diana M Brainard, Anu Osinusi, Lisa Moorehead, Bernard Murray, Kah Hiing John Ling, Robert Perry, Craig Curtis, Eric Lawitz, Kenneth Lasseter and 2 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Mass balance study of [Antimicrobial agents and chemotherapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Erik MogalianGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA. Erik.Mogalian@gilead.com.ORCID 0000-0001-5999-3324
Diana M BrainardGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Anu OsinusiGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Lisa MooreheadGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Bernard MurrayGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Kah Hiing John LingGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
Robert PerryElite Research Institute, Miami, FL, USA.
Craig CurtisCompass Research, Orlando, FL, USA.
Eric LawitzTexas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA.
Kenneth LasseterClinical Pharmacology of Miami, Miami, FL, USA.
Thomas MarburyOrlando Clinical Research Center, Orlando, FL, USA.
Anita MathiasGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe pharmacokinetics and safety of velpatasvir, a potent pangenotypic hepatitis C virus NS5A inhibitor, were evaluated in two hepatic impairment studies: a phase I study in hepatitis C virus-uninfected subjects and a phase III study (ASTRAL-4) in hepatitis C virus-infected patients.

methodsIn the phase I study, subjects with moderate or severe hepatic impairment (Child-Pugh-Turcotte Class B or C), and demographically matched subjects with normal hepatic function received a single dose of velpatasvir 100 mg. Pharmacokinetics and safety assessments were performed, and pharmacokinetic parameters were calculated using non-compartmental methods and summarized using descriptive statistics and compared statistically by geometric least-squares mean ratios and 90% confidence intervals. In ASTRAL-4, subjects with decompensated cirrhosis (Child-Pugh-Turcotte Class B) were randomized to receive treatment with either sofosbuvir/velpatasvir ± ribavirin for 12 weeks or sofosbuvir/velpatasvir for 24 weeks. Pharmacokinetic and safety assessments were performed and pharmacokinetic parameters were calculated using a non-compartmental analysis and summarized using descriptive statistics and were compared to pharmacokinetics from ASTRAL-1 [subjects without cirrhosis or with compensated (Child-Pugh-Turcotte Class A) cirrhosis].

resultsIn the phase I study, plasma exposures (area under the concentration-time curve) were similar in subjects with Child-Pugh-Turcotte Class B (n = 10) or Child-Pugh-Turcotte Class C hepatic impairment (n = 10) compared with normal hepatic function (n = 13). Percent free velpatasvir was similar in subjects without or with any degree of hepatic impairment. In the phase III study, velpatasvir overall exposure (area under the concentration-time curve over the 24-h dosing interval; AUC

conclusionsNo sofosbuvir/velpatasvir dose modification is warranted for patients with any degree of hepatic impairment.

Indexed as

AdolescentAdultAgedAntiviral AgentsBenzimidazolesBenzopyransCarbamatesDrug CombinationsDrug Therapy, CombinationFemaleHepatic InsufficiencyHepatitis CHeterocyclic Compounds, 4 or More RingsHumansLiver CirrhosisMaleAntiviral AgentsBenzimidazolesBenzopyransCarbamatesDrug CombinationsGS331007Heterocyclic Compounds, 4 or More RingsRibavirinSofosbuvirsofosbuvir-velpatasvir drug combinationUridinevelpatasvir

Identifiers

PMID29520729

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.