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Exposure-Efficacy Analyses of Ombitasvir, Paritaprevir/Ritonavir with Dasabuvir ± Ribavirin in HCV Genotype 1-Infected Patients

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Abstract

Background and Objectives

The three-direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir (coadministered with ritonavir [paritaprevir/ritonavir], and dasabuvir (the 3D regimen) ± ribavirin for treatment of HCV genotype 1-infected patients demonstrated efficacy and safety in Phase II and Phase III clinical trials. The relationships between the steady-state exposure (area under the concentration-time curve at steady state and trough concentration at steady state) of the three DAAs and ribavirin with sustained virologic response at 12 weeks after treatment (SVR12) following administration of the 3D regimen in six Phase II/III studies were examined.

Methods

HCV non-cirrhotic genotype 1-infected adult male and female patients (N = 1690) enrolled in the one Phase II study or one of the five Phase III studies were included for graphical analysis. HCV subgenotype 1a-infected patients who received the 3D regimen with ribavirin (approved regimen for that patient population) (N = 615) from the same studies were included in the multivariate logistic regression exposure-response analysis.

Results

Graphical analysis suggested a shallow trend between exposure and % SVR12 for paritaprevir, ombitasvir, and ribavirin exposure but not for dasabuvir exposure. After adjusting for covariate effects, the exposure-response logistic-regression analysis indicated that ombitasvir exposure was the single significant predictor, demonstrating a 1 % change in SVR12 with up to 25 % change in ombitasvir exposure at steady state.

Conclusions

The results of these analyses indicate that the doses selected for the 3D regimen were optimal, achieving high SVR12 rates across the range of exposures observed in the Phase III studies.

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Acknowledgments

The authors thank the clinical sites and investigators and AbbVie study team members for assistance with the conduct of the study. Assistance with datasets was provided by Will He, and assistance with graphs and the study report was provided by Lisa Hernandez; both are employed by AbbVie.

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    Authors and Affiliations

    1. AbbVie, Inc., North Chicago, IL, 60064, USA

      Amit Khatri, Thomas Podsadecki, Walid Awni, Rajeev Menon & Sandeep Dutta

    2. AbbVie Deutschland GmbH & Co KG, Ludwigshafen am Rhein, Germany

      Sven Mensing

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    1. Amit Khatri
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    Corresponding author

    Correspondence to Sandeep Dutta.

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    Funding

    The study was sponsored by AbbVie. AbbVie contributed to the study design, research, and interpretation of data, and the writing, reviewing, and approving of the publication. Medical writing support was provided by Amy Rohrlack, a medical writer employed by AbbVie.

    Conflict of interest

    Amit Khatri is an employee of AbbVie and holds AbbVie stock or stock options. Sven Mensing is an employee of AbbVie and holds AbbVie stock or stock options. Thomas Podsadecki is an employee of AbbVie and holds AbbVie stock or stock options. Walid Awni is an employee of AbbVie and holds AbbVie stock or stock options. Rajeev Menon is an employee of AbbVie and holds AbbVie stock or stock options. Sandeep Dutta is an employee of AbbVie and holds AbbVie stock or stock options.

    Ethical Approval

    The studies were conducted in accordance with the ethical principles set forth in the Declaration of Helsinki and its amendments, International Conference for Harmonisation − Good Clinical Practice guidelines, and local guidelines and regulations. The protocol and informed consent forms were approved by the institutional review board/ethics committee.

    Informed Consent

    Written informed consent was obtained from all patients before being included in the study.

    Additional information

    A. Khatri and S. Mensing contributed equally.

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    Khatri, A., Mensing, S., Podsadecki, T. et al. Exposure-Efficacy Analyses of Ombitasvir, Paritaprevir/Ritonavir with Dasabuvir ± Ribavirin in HCV Genotype 1-Infected Patients. Clin Drug Investig 36, 625–635 (2016). https://doi.org/10.1007/s40261-016-0407-x

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    • DOI: https://doi.org/10.1007/s40261-016-0407-x

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