balapiravir and Hepatitis-C--Chronic

balapiravir has been researched along with Hepatitis-C--Chronic* in 4 studies

Reviews

2 review(s) available for balapiravir and Hepatitis-C--Chronic

ArticleYear
R-1626, a specific oral NS5B polymerase inhibitor of hepatitis C virus.
    IDrugs : the investigational drugs journal, 2008, Volume: 11, Issue:10

    Roche Holding AG is developing R-1626, an oral nucleoside inhibitor of HCV RNA polymerase. R-1626 has been demonstrated to be well absorbed and rapidly converted to the active component R-1479. The compound has demonstrated a strong capacity to inhibit HCV replication in vitro and in vivo, without the rapid development of viral resistance. After 4 weeks of treatment with R-1626 in combination with PEG-IFN plus ribavirin in treatment-naïve patients with genotype 1 HCV infection, HCV RNA could no longer be detected in approximately 74% of patients, compared with 5% of patients treated with PEG-IFN plus ribavirin alone, indicating the high potency of R-1626 to induce HCV RNA viral load reductions. R-1626 was generally well tolerated, although severe side effects of neutropenia were observed at high doses. A phase IIb clinical trial was ongoing at the time of publication to test the efficacy of R-1626 in combination with a standard or lower dose of PEG-IFN and ribavirin in HCV genotype 1-infected patients. Given its potent antiviral effect with an apparent high genetic barrier, R-1626 represents an important advancement in improving the outcome of patients with chronic HCV infection.

    Topics: Administration, Oral; Animals; Antiviral Agents; Drug Evaluation, Preclinical; Drug Resistance, Viral; Drug Therapy, Combination; Enzyme Inhibitors; Hepacivirus; Hepatitis C, Chronic; Humans; Molecular Structure; Nucleosides; Patents as Topic; Prodrugs; RNA, Viral; Structure-Activity Relationship; Treatment Outcome; Viral Load; Viral Nonstructural Proteins

2008
Future treatment options for HCV: double, triple, what is the optimal combination?
    Best practice & research. Clinical gastroenterology, 2008, Volume: 22, Issue:6

    Specifically Targeted Antiviral Therapy against hepatitis C virus (STAT-C) stands for a new era in the treatment of patients with chronic hepatitis C. Results from recent trials with protease and polymerase inhibitors indicate that therapy with a single HCV specific compound will not be sufficient to eradicate hepatitis C virus infection and that combination therapy will be necessary to improve sustained virologic response rates. The search for the optimal combination of STAT-C compounds with peginterferon alfa with or without ribavirin is currently under investigation in several clinical trials. Overall the current studies indicate that peginterferon alfa and ribavirin remain the backbone of antiviral therapy of chronic hepatitis C even in the era of STAT-C. Nevertheless, it can be anticipated that combination of STAT-C compounds with non-overlapping resistance profiles could improve response to antiviral therapy. Promising combinations are protease inhibitors plus nucleoside analogue and non-nucleoside analogue polymerase inhibitors.

    Topics: Antiviral Agents; Cytidine; DNA-Directed RNA Polymerases; Drug Delivery Systems; Drug Resistance, Viral; Drug Therapy, Combination; Forecasting; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Nucleosides; Oligopeptides; Polyethylene Glycols; Prodrugs; Proline; Protease Inhibitors; Pyrimidine Nucleosides; Recombinant Proteins; Ribavirin

2008

Trials

1 trial(s) available for balapiravir and Hepatitis-C--Chronic

ArticleYear
Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C.
    Hepatology (Baltimore, Md.), 2008, Volume: 48, Issue:2

    The nucleoside analog R1479 is a potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro. R1626, a tri-isobutyl ester prodrug of R1479, was developed to increase bioavailability and improve antiviral activity. A multicenter, observer-blinded, randomized, placebo-controlled, multiple ascending dose, phase 1b study was designed to evaluate the safety, pharmacokinetics, and antiviral activity and to potentially identify the maximum tolerated dose of R1626 in patients with chronic hepatitis C. Forty-seven treatment-naïve patients infected with HCV genotype 1 were treated with R1626 orally at doses of 500 mg, 1500 mg, 3000 mg, or 4500 mg or placebo twice daily for 14 days with 14 days of follow-up. Safety, tolerability, pharmacokinetics, and antiviral activity were assessed. Doses up to and including 3000 mg twice daily were well tolerated after 14 days of treatment. There was an increase in frequency of adverse events at the highest dose (4500 mg). Reversible mild to moderate hematological changes were observed with increasing doses. R1626 was efficiently converted to R1479, with dose-proportional pharmacokinetics observed over the entire dose range. The pharmacokinetics of R1479 were linear over the dose range evaluated. Dose-dependent and time-dependent reductions in HCV RNA were observed. Mean decreases (median; range) in viral load after 14 days of treatment with doses of 500, 1500, 3000, and 4500 mg were 0.32 (0.22; 0.01-0.71), 1.2 (0.8; 0.49-2.46), 2.6 (2.7; 1.27-3.93) and 3.7 (4.1; 2.15-4.39) log(10), respectively. No resistance to R1479 was observed after 14 days of treatment with R1626.. These data support further studies of R1626 in combination with peginterferon alfa-2a and ribavirin for the treatment of patients with chronic HCV infection.

    Topics: Adult; Alanine Transaminase; Antiviral Agents; Cytidine; Dose-Response Relationship, Drug; Drug Resistance, Viral; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Male; Middle Aged; Nucleosides; Prodrugs; RNA, Viral; Single-Blind Method; Time Factors; Viral Load

2008

Other Studies

1 other study(ies) available for balapiravir and Hepatitis-C--Chronic

ArticleYear
Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus.
    Antimicrobial agents and chemotherapy, 2016, Volume: 60, Issue:2

    Toxicity has emerged during the clinical development of many but not all nucleotide inhibitors (NI) of hepatitis C virus (HCV). To better understand the mechanism for adverse events, clinically relevant HCV NI were characterized in biochemical and cellular assays, including assays of decreased viability in multiple cell lines and primary cells, interaction with human DNA and RNA polymerases, and inhibition of mitochondrial protein synthesis and respiration. NI that were incorporated by the mitochondrial RNA polymerase (PolRMT) inhibited mitochondrial protein synthesis and showed a corresponding decrease in mitochondrial oxygen consumption in cells. The nucleoside released by the prodrug balapiravir (R1626), 4'-azido cytidine, was a highly selective inhibitor of mitochondrial RNA transcription. The nucleotide prodrug of 2'-C-methyl guanosine, BMS-986094, showed a primary effect on mitochondrial function at submicromolar concentrations, followed by general cytotoxicity. In contrast, NI containing multiple ribose modifications, including the active forms of mericitabine and sofosbuvir, were poor substrates for PolRMT and did not show mitochondrial toxicity in cells. In general, these studies identified the prostate cell line PC-3 as more than an order of magnitude more sensitive to mitochondrial toxicity than the commonly used HepG2 cells. In conclusion, analogous to the role of mitochondrial DNA polymerase gamma in toxicity caused by some 2'-deoxynucleotide analogs, there is an association between HCV NI that interact with PolRMT and the observation of adverse events. More broadly applied, the sensitive methods for detecting mitochondrial toxicity described here may help in the identification of mitochondrial toxicity prior to clinical testing.

    Topics: Antiviral Agents; Cell Line; Deoxycytidine; DNA Polymerase gamma; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; Guanosine Monophosphate; Hepacivirus; Hepatitis C, Chronic; Humans; Mitochondria; Nucleosides; Oxygen Consumption; Protein Biosynthesis; RNA; RNA, Mitochondrial; Sofosbuvir; Transcription, Genetic; Virus Replication

2016