Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12 weeks

Feld, Jordan J.; Moreno, Christophe; Trinh, Roger; Tam, Edward; Bourgeois, Stefan; Horsmans, Yves; Elkhashab, Magdy; Bernstein, David; Younes, Ziad; Reindollar, Robert; Larsen, Lois; Fu, Bo; Howieson, Kevin; Polepally, Akshanth R.; Pangerl, Andreas; Shulman, Nancy S.; Poordad, Fred

doi:10.1016/j.jhep.2015.10.005

Cited by 155 publications

(127 citation statements)

References 30 publications

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“…It is needed for patients with genotype 1a HCV and patients with genotype 4 HCV (16,24,25). The population pharmacokinetic modeling indicates that ribavirin co-administration does not affect the pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, or ritonavir; use of ribavirin was not identified as a covariate in any of the analyses.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies

Mensing

Polepally

König

et al. 2015

AAPS J

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Abstract. Direct-acting antiviral agents (DAAs) are established as the standard of care for chronic hepatitis C virus (HCV) infection. One of the newest additions to the HCV arsenal is an oral three-DAA combination therapy (i.e., the 3D regimen) that does not require concomitant use of pegylated interferon. The clinical development program for the 3D regimen has yielded a robust dataset that is inclusive of various dosing schemes and a diverse patient population. Using data from nine phase 1b/2a/ 2b studies that enrolled patients with HCV genotype 1 infection, population pharmacokinetic models were developed for each component of the 3D regimen (ombitasvir, paritaprevir, ritonavir, and dasabuvir) and for ribavirin, an adjunctive therapy used to enhance therapeutic efficacy in some populations. Formulation effects, accumulation, relative bioavailability, and interactions between DAAs were assessed during model development, and demographic and clinical covariates were identified and evaluated for their effects on drug exposures. Proposed models were assessed via goodness-of-fit plots, visual predictive checks, and bootstrap evaluations. Population pharmacokinetic models adequately described their respective plasma concentration-time data with precise and reliable model parameter estimates and with good predictive performance. Covariates, including age, sex, body weight, cytochrome P450 2C8 inhibitor use, non-Hispanic ethnicity, and creatinine clearance, were associated with apparent clearance and/or apparent volume parameters; however, the magnitude of effect on drug exposure was modest and not considered to be clinically significant. No patient-related or clinical parameters were identified that would necessitate dose adjustment of the 3D regimen in patients with HCV genotype 1 infection.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies

Mensing

Polepally

König

et al. 2015

AAPS J

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“…In clinical studies, the regimen consisting of OBV/PTV/r + DSV ± RBV was highly efficacious to treat HCV GT1a or GT1b infection, including patients with compensated cirrhosis, liver transplant or human immunodeficiency virus 1 (HIV-1) co-infection. The observed SVR12 rate ranged from 92% to 100% (8,(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

et al. 2018

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“…GT-1a infected patients with HCV RNA ≤800,000 IU/ml (5.9 log 10 IU/ml) at baseline and those with HCV RNA >800,000 IU/ml (5.9 log 10 IU/ml), but without NS5A RASs at baseline should receive the FDC Grazoprevir/Elbasvir for 12 weeks without Ribavirin [B1]. These recommendations are based on the results of three phase III RCTs (C-EDGE-TN, C-EDGE-TE, C-EDGECoinfection) [61,62] and a post-hoc analysis of pooled phase II and III clinical trials data [63].…”

Section: Ritonavir-boostedmentioning

confidence: 99%

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

Gheorghe

Sporea

Iacob

et al. 2017

JGLD

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Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

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Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12 weeks

Abstract: The HCV regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir without ribavirin for 12weeks achieved 100% SVR12 and was well tolerated in HCV genotype 1b-infected patients with cirrhosis, suggesting that this 12-week ribavirin-free regimen is sufficient in this population.

Cited by 155 publications

References 30 publications

Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies

Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies

Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

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