A Drug-Drug Interaction Study of Ketoconazole, Rifampicin and Ritonavir-Boosted Atazanavir With Single-Dose RO5093151 in Healthy Volunteers

A Randomized, Single-center, Open-label, One-sequence, Two-period Crossover Study in 3 Parts to Investigate the Effects of Multiple Doses of Ketoconazole (Part 1), Rifampicin (Part 2), and Ritonavir-boosted Atazanavir (Part 3) on the PK of a Single Dose of RO5093151 in Healthy Female & Male Subjects

This randomized, single-center, open-label, one-sequence, two-period crossover study in three parts will assess the effects of multiple doses of ketoconazole, rifampicin and ritonavir-boosted atazanavir on the pharmacokinetics of a single dose of RO5093151 in healthy male and female volunteers. In Period 1, subjects will receive a single oral dose of RO5093151. In Period 2, subjects will receive a single oral dose of RO5093151 and multiple oral doses of either ketoconazole, rifampicin or ritonavir-boosted atazanavir. Anticipated time on study is up to 8.5 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: ketoconazole; Drug: RO5093151; Drug: rifampicin; Drug: atazanavir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Merritt Island, Florida, United States, 32953

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects, 18 to 65 years of age. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history and complete physical examination
• Body mass index (BMI) 18 to 30 kg/m2
• Females of child-bearing potential must agree to use two effective methods of contraception, including a barrier method and an intrauterine non-hormonal device (set in place at least 3 months before first dosing) for the duration of the study and at least 1 month after last dosing
• Non-smoker for at least 90 days prior to screening

Exclusion Criteria:

• Pregnant or lactating females
• History of drug abuse in the past 2 years, or suspicion of regular consumption of drugs of abuse, or positive result on drugs of abuse test
• History of alcoholism in the past 2 years, or positive alcohol test
• Positive for hepatitis B, hepatitis C or HIV infection
• Systemic , topical, intranasal or inhaled corticosteroid therapy for more than 2 weeks within 3 months prior to screening
• Participation in an investigational drug or device study within 90 days prior to screening

Study Plan

How is the study designed?

Design Details

• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Ketoconazole DDI	Drug: ketoconazole; Multiple oral doses; Drug: RO5093151; Single oral dose
Experimental: 2 Rifampicin DDI	Drug: RO5093151; Single oral dose; Drug: rifampicin; Multiple oral doses
Experimental: 3 ATZ/r DDI	Drug: RO5093151; Single oral dose; Drug: atazanavir; Multiple oral doses; Drug: ritonavir; Multiple oral doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Effect of multiple doses of ketoconazole on single-dose pharmacokinetics of RO5093151 and metabolites: Area under the concentration-time curve (AUC)	Pre-dose and up to 72 hours post-dose
Part 2: Effect of multiple doses of rifampicin on single-dose pharmacokinetics of RO5093151 and metabolites: Area under the concentration-time curve (AUC)	Pre-dose and up to 72 hours post-dose
Part 3: Effect of multiple doses of ritonavir-boosted atazanavir on single-dose pharmacokinetics of RO5093151 and metabolites: Area under the concentration-time curve (AUC)	Pre-dose and up to 72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 6 month
RO5093151 metabolites: Plasma/urine concentrations	Pre-dose and up to 72 hours post-dose
Pharmacodynamics: Area under the effect curve (AUEC) for plasma cortisol/cortisone (Part 1 only)	Pre-dose and up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 3, 2012
• First Submitted That Met QC Criteria: May 3, 2012
• First Posted (Estimate): May 4, 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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Ritonavir; Ketoconazole; Rifampin; Atazanavir Sulfate
• Other Study ID Numbers: BP27852