Cargando…
Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study
BACKGROUND: Hepatitis C virus (HCV) infection is increasing among pregnant women because of the opioid epidemic, yet there are no interventions to reduce perinatal HCV transmission or to treat HCV during pregnancy. Physiological changes in pregnancy alter the pharmacokinetics of some medications; th...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491553/ https://www.ncbi.nlm.nih.gov/pubmed/32939459 http://dx.doi.org/10.1016/S2666-5247(20)30062-8 |
_version_ | 1783582239825592320 |
---|---|
author | Chappell, Catherine A Scarsi, Kimberly K Kirby, Brian J Suri, Vithika Gaggar, Anuj Bogen, Debra L Macio, Ingrid S Meyn, Leslie A Bunge, Katherine E Krans, Elizabeth E Hillier, Sharon L |
author_facet | Chappell, Catherine A Scarsi, Kimberly K Kirby, Brian J Suri, Vithika Gaggar, Anuj Bogen, Debra L Macio, Ingrid S Meyn, Leslie A Bunge, Katherine E Krans, Elizabeth E Hillier, Sharon L |
author_sort | Chappell, Catherine A |
collection | PubMed |
description | BACKGROUND: Hepatitis C virus (HCV) infection is increasing among pregnant women because of the opioid epidemic, yet there are no interventions to reduce perinatal HCV transmission or to treat HCV during pregnancy. Physiological changes in pregnancy alter the pharmacokinetics of some medications; thus, our aim was to compare the pharmacokinetic parameters of ledipasvir 90 mg plus sofosbuvir 400 mg during pregnancy with non-pregnant women. METHODS: This was an open-label, phase 1 study of pregnant women with genotype 1 HCV infection and their infants. A reference group of women who had participated in pharmacokinetic studies of ledipasvir–sofosbuvir during phase 2 and 3 trials was used. Participants were enrolled at Magee-Womens Hospital (Pittsburgh, PA, USA) between 23 and 24 weeks’ gestation and had a 12-week course of oral ledipasvir–sofosbuvir (daily 90 mg ledipasvir plus 400 mg sofosbuvir). Three 12-h intensive pharmacokinetic visits were done at 25–26, 29–30, and 33–34 weeks’ gestation and individual pharmacokinetics were summarised by geometric mean across the three visits. The primary outcome, analysed in all participants without suspected dosing errors, was the ledipasvir–sofosbuvir area under the concentration–time curve of the dosing interval (AUC(tau)) during pregnancy compared with the reference group by geometric mean ratio. This study is registered with ClinicalTrials.gov, NCT02683005. FINDINGS: From Oct 1, 2016, to Sept 30, 2018, 29 pregnant women were screened and nine (31%) were enrolled. Eight (89%) women were included in the primary analysis. Ledipasvir and sofosbuvir exposures were similar in the pregnant women versus the non-pregnant reference group (geometric mean ratio of AUC(tau) ledipasvir 89·3% [90% CI 68·7–116·1]; sofosbuvir 91·1% [78·0–106·3]). INTERPRETATION: Ledipasvir–sofosbuvir was safe and effective without clinically meaningful differences in drug exposure among pregnant versus non-pregnant women. FUNDING: National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health/Office of Research on Women’s Health, and Gilead Sciences. |
format | Online Article Text |
id | pubmed-7491553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-74915532020-09-15 Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study Chappell, Catherine A Scarsi, Kimberly K Kirby, Brian J Suri, Vithika Gaggar, Anuj Bogen, Debra L Macio, Ingrid S Meyn, Leslie A Bunge, Katherine E Krans, Elizabeth E Hillier, Sharon L Lancet Microbe Article BACKGROUND: Hepatitis C virus (HCV) infection is increasing among pregnant women because of the opioid epidemic, yet there are no interventions to reduce perinatal HCV transmission or to treat HCV during pregnancy. Physiological changes in pregnancy alter the pharmacokinetics of some medications; thus, our aim was to compare the pharmacokinetic parameters of ledipasvir 90 mg plus sofosbuvir 400 mg during pregnancy with non-pregnant women. METHODS: This was an open-label, phase 1 study of pregnant women with genotype 1 HCV infection and their infants. A reference group of women who had participated in pharmacokinetic studies of ledipasvir–sofosbuvir during phase 2 and 3 trials was used. Participants were enrolled at Magee-Womens Hospital (Pittsburgh, PA, USA) between 23 and 24 weeks’ gestation and had a 12-week course of oral ledipasvir–sofosbuvir (daily 90 mg ledipasvir plus 400 mg sofosbuvir). Three 12-h intensive pharmacokinetic visits were done at 25–26, 29–30, and 33–34 weeks’ gestation and individual pharmacokinetics were summarised by geometric mean across the three visits. The primary outcome, analysed in all participants without suspected dosing errors, was the ledipasvir–sofosbuvir area under the concentration–time curve of the dosing interval (AUC(tau)) during pregnancy compared with the reference group by geometric mean ratio. This study is registered with ClinicalTrials.gov, NCT02683005. FINDINGS: From Oct 1, 2016, to Sept 30, 2018, 29 pregnant women were screened and nine (31%) were enrolled. Eight (89%) women were included in the primary analysis. Ledipasvir and sofosbuvir exposures were similar in the pregnant women versus the non-pregnant reference group (geometric mean ratio of AUC(tau) ledipasvir 89·3% [90% CI 68·7–116·1]; sofosbuvir 91·1% [78·0–106·3]). INTERPRETATION: Ledipasvir–sofosbuvir was safe and effective without clinically meaningful differences in drug exposure among pregnant versus non-pregnant women. FUNDING: National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health/Office of Research on Women’s Health, and Gilead Sciences. 2020-07-27 2020-09 /pmc/articles/PMC7491553/ /pubmed/32939459 http://dx.doi.org/10.1016/S2666-5247(20)30062-8 Text en This is an Open Access article under the CC BY-NC-ND 4.0 license.http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chappell, Catherine A Scarsi, Kimberly K Kirby, Brian J Suri, Vithika Gaggar, Anuj Bogen, Debra L Macio, Ingrid S Meyn, Leslie A Bunge, Katherine E Krans, Elizabeth E Hillier, Sharon L Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title | Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title_full | Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title_fullStr | Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title_full_unstemmed | Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title_short | Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study |
title_sort | ledipasvir plus sofosbuvir in pregnant women with hepatitis c virus infection: a phase 1 pharmacokinetic study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491553/ https://www.ncbi.nlm.nih.gov/pubmed/32939459 http://dx.doi.org/10.1016/S2666-5247(20)30062-8 |
work_keys_str_mv | AT chappellcatherinea ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT scarsikimberlyk ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT kirbybrianj ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT surivithika ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT gaggaranuj ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT bogendebral ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT macioingrids ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT meynlesliea ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT bungekatherinee ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT kranselizabethe ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy AT hilliersharonl ledipasvirplussofosbuvirinpregnantwomenwithhepatitiscvirusinfectionaphase1pharmacokineticstudy |