title: Exposure-Efficacy Analyses of Ombitasvir, Paritaprevir/Ritonavir with Dasabuvir ± Ribavirin in HCV Genotype 1-Infected Patients.
abstract: OBJECTIVE
  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.
authors.affiliation: AbbVie, Inc., North Chicago, IL, 60064, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Khatri
authors.affiliation: AbbVie Deutschland GmbH & Co KG, Ludwigshafen am Rhein, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mensing
authors.affiliation: AbbVie, Inc., North Chicago, IL, 60064, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
authors.affiliation: AbbVie, Inc., North Chicago, IL, 60064, USA.
authors.forename: Walid
authors.initials: W
authors.lastname: Awni
authors.affiliation: AbbVie, Inc., North Chicago, IL, 60064, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Menon
authors.affiliation: AbbVie, Inc., North Chicago, IL, 60064, USA. sandeep.dutta@abbvie.com.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
mesh_terms: D015081:2-Naphthylamine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014633:Valine; D055815:Young Adult
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir