| Title |
Pharmacokinetics and Safety of Velpatasvir and Sofosbuvir/Velpatasvir in Subjects with Hepatic Impairment
|
|---|---|
| Published in |
Clinical Pharmacokinetics, March 2018
|
| DOI | 10.1007/s40262-018-0645-6 |
| Pubmed ID | |
| Authors |
Erik Mogalian, Diana M. Brainard, Anu Osinusi, Lisa Moorehead, Bernard Murray, Kah Hiing John Ling, Robert Perry, Craig Curtis, Eric Lawitz, Kenneth Lasseter, Thomas Marbury, Anita Mathias |
| Abstract |
The 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. In 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]. In 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; AUCtau) was similar and sofosbuvir exposures were higher (~ 100%) for patients with Child-Pugh-Turcotte Class B hepatic impairment compared with the ASTRAL-1 population, which was not considered clinically relevant. No sofosbuvir/velpatasvir dose modification is warranted for patients with any degree of hepatic impairment. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 33 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 21% |
| Student > Master | 5 | 15% |
| Student > Bachelor | 3 | 9% |
| Other | 3 | 9% |
| Student > Doctoral Student | 3 | 9% |
| Other | 1 | 3% |
| Unknown | 11 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 33% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 12% |
| Biochemistry, Genetics and Molecular Biology | 1 | 3% |
| Immunology and Microbiology | 1 | 3% |
| Agricultural and Biological Sciences | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 13 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 March 2018.
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#18,590,133
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Outputs from Clinical Pharmacokinetics
#1,320
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Outputs of similar age from Clinical Pharmacokinetics
#24
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