| Autor: |
Polepally AR; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA., Wang H; Biometrics, AbbVie Inc, North Chicago, Illinois, USA., Marroum PJ; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA., Minocha M; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA., Hosmane B; Biometrics, AbbVie Inc, North Chicago, Illinois, USA., Khatri A; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA., Mensing S; Clinical Pharmacology and Pharmacometrics, AbbVie Deutschland GmbH & Co, Ludwigshafen am Rhein, Germany., Podsadecki TJ; Infectious Disease Development, AbbVie Inc, North Chicago, Illinois, USA., Cohen DE; Infectious Disease Development, AbbVie Inc, North Chicago, Illinois, USA., Awni WM; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA., Menon RM; Clinical Pharmacokinetics and Pharmacodynamics, AbbVie Inc, North Chicago, Illinois, USA. rajeev.menon@abbvie.com. |
| Abstrakt: |
The triple direct-acting antiviral (3-DAA) regimen (two co-formulated tablets of ombitasvir/paritaprevir/ritonavir once daily and one tablet of dasabuvir twice daily) for patients with hepatitis C virus (HCV) genotype 1 infection has been reformulated for once-daily administration containing all three active DAAs (3QD regimen). Two bioequivalence studies compared the 3-DAA and 3QD regimens. In study 1, fed, single-, and multiple-dose crossover comparisons revealed exposures for drug components that were slightly outside the bioequivalence criteria, i.e., 21 to 29% lower dasabuvir C trough , paritaprevir C max , and ritonavir C max . In study 2, fed and fasted single-dose crossover comparisons demonstrated a large impact of food on exposures, confirming the product's labeling requirement for administration only with food, and revealed a lack of bioequivalence under fasting conditions. Exposure-response analyses using efficacy data from phase 2/3 studies of the 3-DAA regimen demonstrated that the lower dasabuvir C trough for the 3QD regimen (under fed condition) would have minimal impact on sustained virologic response at week 12 post-treatment (SVR 12 ). Thus, the pharmacodynamic similarity between the regimens was established and the analyses provided the basis for regulatory approval of the 3QD regimen to treat patients with chronic HCV genotype 1 infection. |
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