A Drug-Drug Interaction Study of Ketoconazole, Rifampicin and Ritonavir-Boosted Atazanavir With Single-Dose RO5093151 in Healthy Volunteers
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
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) [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
- 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]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Merritt Island | Florida | United States | 32953 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BP27852