PMID- 31254392
OWN - NLM
STAT- MEDLINE
DCOM- 20201001
LR  - 20201001
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 71
IP  - 2
DP  - 2020 Feb
TI  - Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents 
      With Chronic Hepatitis C Virus: Part 1 of the DORA Study.
PG  - 456-462
LID - 10.1002/hep.30840 [doi]
AB  - The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to 
      treat adults with chronic hepatitis C virus (HCV) infection and has yielded high 
      cure rates in adults in clinical trials. Approved treatment options for 
      pediatrics may include ribavirin. A pangenotypic regimen for pediatric patients 
      remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, open-label 
      study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in 
      pediatric patients with chronic HCV. This analysis includes Part 1 of the study, 
      conducted in adolescent patients 12-17 years of age given the adult regimen of 
      G/P (300 mg/120 mg) once daily for 8-16 weeks according to the indication 
      durations used in adults. Patients were either treatment naive or experienced 
      with interferon-based regimens. The primary PK endpoint was steady-state 
      exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was 
      sustained virologic response 12 weeks after treatment (SVR12). The secondary 
      efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. 
      Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients 
      infected with genotypes 1, 2, 3, or 4, of whom 47 were administered G/P. All 47 
      patients (100%) achieved SVR12. No on-treatment virologic failures or relapses 
      occurred. PK exposures of glecaprevir and pibrentasvir were comparable to 
      exposures in adults. No adverse events (AEs) led to treatment discontinuation, 
      and no serious AEs occurred. Conclusion: Adolescent patients with chronic HCV 
      infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 
      rate, and safety profile consistent with that in adults. This pangenotypic 
      regimen demonstrated 100% efficacy within the adolescent population in as little 
      as 8 weeks of treatment.
CI  - (c) 2019 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of 
      American Association for the Study of Liver Diseases.
FAU - Jonas, Maureen M
AU  - Jonas MM
AD  - Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's 
      Hospital, Boston, MA.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA.
FAU - Squires, Robert H
AU  - Squires RH
AD  - Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital 
      of Pittsburgh, Pittsburgh, PA.
AD  - Department of Pediatrics, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA.
FAU - Rhee, Susan M
AU  - Rhee SM
AD  - AbbVie Inc., North Chicago, IL.
FAU - Lin, Chih-Wei
AU  - Lin CW
AD  - Amgen Inc., Thousand Oaks, CA.
FAU - Bessho, Kazuhiko
AU  - Bessho K
AD  - Osaka University Hospital, Osaka, Japan.
FAU - Feiterna-Sperling, Cornelia
AU  - Feiterna-Sperling C
AD  - Charite - Universitaetsmedizin Berlin, Berlin, Germany.
FAU - Hierro, Loreto
AU  - Hierro L
AD  - Hospital Universitario La Paz, Madrid, Spain.
FAU - Kelly, Deirdre
AU  - Kelly D
AD  - Birmingham Women's & Children's Hospital, Birmingham, United Kingdom.
FAU - Ling, Simon C
AU  - Ling SC
AD  - Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick 
      Children, and Department of Paediatrics, University of Toronto, Toronto, Ontario, 
      Canada.
FAU - Strokova, Tatiana
AU  - Strokova T
AD  - Federal Research Centre of Nutrition and Biotechnology, Moscow, Russian 
      Federation.
FAU - Del Valle-Segarra, Antonio
AU  - Del Valle-Segarra A
AD  - San Jorge Children's Hospital, San Juan, Puerto Rico.
FAU - Lovell, Sandra
AU  - Lovell S
AD  - AbbVie Inc., North Chicago, IL.
FAU - Liu, Wei
AU  - Liu W
AD  - AbbVie Inc., North Chicago, IL.
FAU - Ng, Teresa I
AU  - Ng TI
AD  - AbbVie Inc., North Chicago, IL.
FAU - Porcalla, Ariel
AU  - Porcalla A
AD  - AbbVie Inc., North Chicago, IL.
FAU - Gonzalez, Yuri Sanchez
AU  - Gonzalez YS
AD  - AbbVie Inc., North Chicago, IL.
FAU - Burroughs, Margaret
AU  - Burroughs M
AD  - AbbVie Inc., North Chicago, IL.
FAU - Sokal, Etienne
AU  - Sokal E
AUID- ORCID: 0000-0001-5597-4708
AD  - Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, 
      Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT03067129
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190813
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Benzimidazoles)
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrrolidines)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0 (glecaprevir and pibrentasvir)
SB  - IM
MH  - Adolescent
MH  - Benzimidazoles/adverse effects/*pharmacokinetics/*therapeutic use
MH  - Child
MH  - Drug Combinations
MH  - Female
MH  - Hepatitis C, Chronic/*drug therapy
MH  - Humans
MH  - Male
MH  - Pyrrolidines/adverse effects/*pharmacokinetics/*therapeutic use
MH  - Quinoxalines/adverse effects/*pharmacokinetics/*therapeutic use
MH  - Sulfonamides/adverse effects/*pharmacokinetics/*therapeutic use
MH  - Treatment Outcome
PMC - PMC7028097
EDAT- 2019/06/30 06:00
MHDA- 2020/10/02 06:00
PMCR- 2020/02/18
CRDT- 2019/06/30 06:00
PHST- 2019/04/18 00:00 [received]
PHST- 2019/06/25 00:00 [accepted]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
PHST- 2019/06/30 06:00 [entrez]
PHST- 2020/02/18 00:00 [pmc-release]
AID - HEP30840 [pii]
AID - 10.1002/hep.30840 [doi]
PST - ppublish
SO  - Hepatology. 2020 Feb;71(2):456-462. doi: 10.1002/hep.30840. Epub 2019 Aug 13.