PMID- 32451952 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20211204 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 37 IP - 7 DP - 2020 Jul TI - Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3-11 Years with Hepatitis C Genotype 1a. PG - 3299-3310 LID - 10.1007/s12325-020-01389-9 [doi] AB - INTRODUCTION: To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1. METHODS: This is an ongoing, open-label, Phase 2/3 study in children 3-11 years old infected with HCV GT1 who were HCV treatment-naive and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters. RESULTS: Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3-8 years old and 12 were 9-11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1-99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade >/= 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation. CONCLUSION: The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3-11 years of age. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02486406. FAU - Rosenthal, Philip AU - Rosenthal P AD - Department of Pediatrics, University of California, San Francisco, CA, USA. PROSENTH@ucsf.edu. FAU - Narkewicz, Michael R AU - Narkewicz MR AD - Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA. FAU - Yao, Betty B AU - Yao BB AD - AbbVie Inc., North Chicago, IL, USA. FAU - Jolley, Christopher D AU - Jolley CD AD - Department of Pediatrics, Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA. FAU - Lobritto, Steven J AU - Lobritto SJ AD - NewYork Presbyterian, Morgan Stanley Children's Hospital and Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA. FAU - Wen, Jessica AU - Wen J AD - Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA. FAU - Molleston, Jean P AU - Molleston JP AD - Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN, USA. FAU - Hsu, Evelyn K AU - Hsu EK AD - Seattle Children's Hospital and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. FAU - Jonas, Maureen M AU - Jonas MM AD - Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. FAU - Zha, Jiuhong AU - Zha J AD - AbbVie Inc., North Chicago, IL, USA. FAU - Liu, Li AU - Liu L AD - AbbVie Inc., North Chicago, IL, USA. FAU - Leung, Daniel H AU - Leung DH AD - Baylor College of Medicine, Gastroenterology, Hepatology, and Nutrition, Texas Children's Liver Center, Houston, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT02486406 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200525 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Anilides) RN - 0 (Antiviral Agents) RN - 0 (Carbamates) RN - 0 (Cyclopropanes) RN - 0 (Cytochrome P-450 CYP3A Inhibitors) RN - 0 (Lactams, Macrocyclic) RN - 0 (Sulfonamides) RN - 0 (Tablets) RN - 2302768XJ8 (ombitasvir) RN - 49717AWG6K (Ribavirin) RN - 56HH86ZVCT (Uracil) RN - 9DLQ4CIU6V (Proline) RN - CKR7XL41N4 (2-Naphthylamine) RN - DE54EQW8T1 (dasabuvir) RN - HG18B9YRS7 (Valine) RN - O3J8G9O825 (Ritonavir) RN - OU2YM37K86 (paritaprevir) MH - 2-Naphthylamine MH - Anilides/*therapeutic use MH - Antiviral Agents/*therapeutic use MH - Carbamates/*therapeutic use MH - Child MH - Child, Preschool MH - Cyclopropanes/*therapeutic use MH - Cytochrome P-450 CYP3A Inhibitors/*therapeutic use MH - Drug Therapy, Combination MH - Female MH - Genotype MH - Hepacivirus/drug effects/genetics MH - Hepatitis C, Chronic/*drug therapy MH - Humans MH - Lactams, Macrocyclic/*therapeutic use MH - Male MH - Proline/*analogs & derivatives/therapeutic use MH - Ribavirin/*therapeutic use MH - Ritonavir/*therapeutic use MH - Sulfonamides/*therapeutic use MH - Tablets MH - Uracil/*analogs & derivatives/therapeutic use MH - Valine PMC - PMC7467405 OTO - NOTNLM OT - Efficacy OT - Hepatology OT - Interferon-free DAA regimens OT - Pediatrics OT - Pharmacokinetics OT - Safety EDAT- 2020/05/27 06:00 MHDA- 2021/02/02 06:00 PMCR- 2020/05/25 CRDT- 2020/05/27 06:00 PHST- 2020/03/17 00:00 [received] PHST- 2020/05/27 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] PHST- 2020/05/27 06:00 [entrez] PHST- 2020/05/25 00:00 [pmc-release] AID - 10.1007/s12325-020-01389-9 [pii] AID - 1389 [pii] AID - 10.1007/s12325-020-01389-9 [doi] PST - ppublish SO - Adv Ther. 2020 Jul;37(7):3299-3310. doi: 10.1007/s12325-020-01389-9. Epub 2020 May 25.