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

Study Overview
=================
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.

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

Conditions
-----------------
Healthy Volunteer

Intervention / Treatment
-----------------
* Drug: RO5093151
* Drug: atazanavir
* Drug: ketoconazole
* Drug: rifampicin
* Drug: ritonavir


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Ketoconazole DDI<br> | Drug: RO5093151<br>* Single oral dose<br>Drug: ketoconazole<br>* Multiple oral doses<br>|
| Experimental: 2 Rifampicin DDI<br> | Drug: RO5093151<br>* Single oral dose<br>Drug: rifampicin<br>* Multiple oral doses<br>|
| Experimental: 3 ATZ/r DDI<br> | Drug: RO5093151<br>* Single oral dose<br>Drug: atazanavir<br>* Multiple oral doses<br>Drug: ritonavir<br>* Multiple oral doses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |