A Pharmacokinetic And Bioavailability Study of Intravenous Danoprevir in Healthy Volunteers

A Three-Part Study Evaluating the Pharmacokinetics of Intravenous (IV) Danoprevir (DNV)/Oral Low-Dose Ritonavir (RTV), the Absolute Bioavailability of DNV With and Without Oral Low-Dose RTV, and the Effect of Oral Cyclosporine on IV DNV/Oral Low-Dose RTV in Healthy Adult Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: placebo; Drug: danoprevir; Drug: danoprevir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9471 GP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: iv danoprevir	Drug: danoprevir; single iv infusion; Drug: danoprevir; single oral dose; Drug: ritonavir; oral doses
PLACEBO_COMPARATOR: Part 1: placebo	Drug: placebo; single iv infusion; Drug: ritonavir; oral doses
EXPERIMENTAL: Part 2 A: iv danoprevir	Drug: danoprevir; single iv infusion; Drug: danoprevir; single oral dose; Drug: ritonavir; oral doses
ACTIVE_COMPARATOR: Part 2 B: oral danoprevir	Drug: danoprevir; single iv infusion; Drug: danoprevir; single oral dose; Drug: ritonavir; oral doses
ACTIVE_COMPARATOR: Part 2 C: ritonavir	Drug: ritonavir; oral doses
EXPERIMENTAL: Part 3 D: iv danoprevir	Drug: danoprevir; single iv infusion; Drug: danoprevir; single oral dose; Drug: ritonavir; oral doses
EXPERIMENTAL: Part 3 E: iv danoprevir + cyclosporine	Drug: danoprevir; single iv infusion; Drug: danoprevir; single oral dose; Drug: ritonavir; oral doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics: Area under the concentration-time curve (AUC)	Pre-dose and up to 12 hours post-dose
Safety: Incidence of adverse events	approximately 7 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: July 27, 2012
• First Submitted That Met QC Criteria: July 27, 2012
• First Posted (ESTIMATE): July 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lactams
• Other Study ID Numbers: NP28297; 2012-000470-40 (EUDRACT_NUMBER)