A Pharmacokinetic And Bioavailability Study of Intravenous Danoprevir in Healthy Volunteers

• Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 7 months ] [ Designated as safety issue: No ]

This three-part study will evaluate the pharmacokinetics and bioavailability of intravenous danoprevir with and without low-dose oral ritonavir, and the effect of oral cyclosporine on the pharmacokinetics of intravenous danoprevir with ritonavir in healthy volunteers.

• Drug: danoprevir
  single iv infusion
• Drug: danoprevir
  single oral dose
• Drug: ritonavir
  oral doses
• Drug: placebo
  single iv infusion

• Experimental: Part 1: iv danoprevir
  Interventions:

  • Drug: danoprevir
  • Drug: ritonavir
• Placebo Comparator: Part 1: placebo
  Interventions:

  • Drug: ritonavir
  • Drug: placebo
• Experimental: Part 2 A: iv danoprevir
  Interventions:

  • Drug: danoprevir
  • Drug: ritonavir
• Active Comparator: Part 2 B: oral danoprevir
  Interventions:

  • Drug: danoprevir
  • Drug: ritonavir
• Active Comparator: Part 2 C: ritonavir
  Intervention: Drug: ritonavir
• Experimental: Part 3 D: iv danoprevir
  Interventions:

  • Drug: danoprevir
  • Drug: ritonavir
• Experimental: Part 3 E: iv danoprevir + cyclosporine
  Interventions:

  • Drug: danoprevir
  • Drug: ritonavir

Inclusion Criteria:

• Adult healthy male and female nonsmoking volunteers, 18 to 55 years of age inclusive; healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history and a complete physical examination

Exclusion Criteria:

• Pregnant or lactating women or males with female partners who are pregnant or lactating
• Positive results for drugs of abuse at screening or prior to admission to the clinical site during any study period
• Positive for hepatitis B, hepatitis C or HIV infection