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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01591850
First received: May 3, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Healthy Volunteer
Drug: RO5093151
Drug: ketoconazole
Drug: rifampicin
Drug: atazanavir
Drug: ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Part 1: Effect of multiple doses of ketoconazole on single-dose pharmacokinetics of RO5093151 and metabolites: Area under the concentration-time curve (AUC) [ Time Frame: Pre-dose and up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Part 2: Effect of multiple doses of rifampicin on single-dose pharmacokinetics of RO5093151 and metabolites: Area under the concentration-time curve (AUC) [ Time Frame: Pre-dose and up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Pre-dose and up to 72 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: approximately 6 month ] [ Designated as safety issue: No ]
  • RO5093151 metabolites: Plasma/urine concentrations [ Time Frame: Pre-dose and up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacodynamics: Area under the effect curve (AUEC) for plasma cortisol/cortisone (Part 1 only) [ Time Frame: Pre-dose and up to 24 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 51
Study Start Date: September 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Ketoconazole DDI Drug: RO5093151
Single oral dose
Drug: ketoconazole
Multiple oral doses
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01591850

Locations
United States, Florida
Merritt Island, Florida, United States, 32953
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01591850     History of Changes
Other Study ID Numbers: BP27852
Study First Received: May 3, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ketoconazole
Atazanavir
Rifampin
Ritonavir
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on April 16, 2014