Effect of Multiple Dosing With BI 201335 on the Pharmacokinetics of Darunavir Co-administered With Ritonavir in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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The objective of the current study is to investigate the effect of multiple oral daily doses of BI 201335 on the steady-state pharmacokinetics of darunavir co-administered with ritonavir.

Official Title
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Effect of Multiple Dosing With 240 mg QD BI 201335 on the Steady-state Pharmacokinetics of 800 mg QD Darunavir Coadministered With 100 mg QD Ritonavir (DRV/r) in Healthy Male and Female Volunteers (an Open-label, Multiple-dose, Single Group, Single Fixed Sequence Phase I Study)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Darunavir
* Drug: Ritonavir
* Drug: BI 201335


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male and female subjects according to the following criteria: medical history, physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram (ECG), clinical laboratory tests Age 18 to 55 years (incl.) Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.) and weight greater than 50 kg Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. Exclusion criteria: Any finding of the medical examination (including blood pressure (BP), pulse rate (PR) and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders History of photosensitivity or recurrent rash. Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes) Inability to refrain from smoking on trial days Alcohol abuse (more than 30 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) ALT outside the normal range or any other laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions Positive serology tests for Human immunodeficiency virus (HIV) and hepatitis B / C virus Vulnerable subjects (e.g. persons kept in detention)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 201335<br>capsule for oral administration | Drug: BI 201335<br> <br> |
| Experimental: Darunavir 400 mg<br>tablet for oral administration | Drug: Darunavir<br>* 400 mg tablet for oral administration<br>|
| Experimental: Ritonavir 100 mg<br>tablet for oral administration | Drug: Ritonavir<br>* tablet for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss of Darunavir | area under the concentration-time curve of the analyte in plasma at steadystate over a uniform dosing interval τ of darunavir. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | 
| Cτ,ss of Darunavir | concentration of the analyte in plasma at steady-state after a uniform dosing interval τ=24h of darunavir | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | 
| Cmax,ss of Darunavir | maximum measured concentration of the analyte in plasma at steady-state | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax,ss of Darunavir | time from last dosing to maximum concentration of the analyte in plasma at steady state | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r) |