A Study of Drug-Drug Interaction Between Danoprevir/Low-Dose Ritonavir and Raltegravir in Healthy Volunteers

A Study to Evaluate the Potential Drug-Drug Interaction Between Danoprevir/Low-Dose Ritonavir When Given With Raltegravir in Healthy Adult Volunteers

This open-label, multiple dose, single sequence crossover study will evaluate the drug-drug interaction between danoprevir/low-dose ritonavir and raltegravir in healthy volunteers. Subjects will receive raltegravir on Days 1-4 and, after a washout period of 3 days, danoprevir and low-dose ritonavir on Days 8-21, in combination with raltegravir on Days 18-21.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219

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:

• Healthy non-smoking male and female adults, 18 - 55 years of age, inclusive
• Healthy status defined by absence of evidence of any active or chronic disease
• Medical history without major, recent, or ongoing pathology
• Weight >/= 50.0 kg
• Body mass index (BMI) 18.0 - 32-0 kg/m2
• Willingness to abstain from alcohol, xanthine-containing beverages or food (e.g. coffee, tea, cola, chocolate, "energy drinks") from 48 hours prior to entry in the clinical site until discharge
• Females of child-bearing potential and males and their female partners of child-bearing potential must agree to use 2 forms of contraception, one of which must be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception are condom and diaphragm; acceptable non-barrier forms of contraception for this study are non-hormonal intrauterine device (IUD) and/or spermicide

Exclusion Criteria:

• Pregnant or lactating females or males with female partners who are pregnant or lactating
• Any history of clinically significant cardiovascular or cerebrovascular disease, hypertension, and/or infections
• Positive test 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
• Current smokers or subjects who have discontinued smoking less than 6 months prior to first dose of study medication
• Use of hormonal contraceptives within 30 days before the first dose of study medication
• History of clinically significant drug-related allergy (such as anaphylaxis) or hepatotoxicity

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Period 1 Control	Drug: raltegravir; 400 mg q12h Days 1-4 and 18-21
Experimental: Period 2 danoprevir/ritonavir	Drug: raltegravir; 400 mg q12h Days 1-4 and 18-21; Drug: danoprevir; 100 mg q12h Days 8-21; Drug: ritonavir; 100 mg q12h Days 8-21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of steady-state ritonavir-boosted danoprevir on steady-state raltegravir pharmacokinetics: Area under the concentration-time curve (AUC)	approximately 2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 2 months
Effect of steady-state raltegravir on danoprevir/ritonavir pharmacokinetics: Area under the concentration-time curve (AUC)	Pre-dose Days 8. 14, 15, 16 and 20, pre-and up to 24 h post-dose Days 17 and 21

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: February 10, 2012
• First Posted (Estimate): February 13, 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; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir
• Other Study ID Numbers: NP28088