Pharmacokinetics of Single Doses of BILR 355 BS Given With Ritonavir in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
Assessment of the effect of two times oral 100 mg ritonavir capsules on pharmacokinetics of a single dose of BILR 355 BS dissolved in PEG 400

Official Title
-----------------
An Open Study to Investigate the Effect of Two Times Oral 100 mg Ritonavir Capsules on Pharmacokinetics of Single Doses of BILR 355 BS (Dose Steps: 5 and 12.5 mg) Dissolved in 5 mL PEG 400 After Oral Administration in Healthy Male Volunteers, and a Double Blind, Placebo Controlled Study for Doses From 25 mg to 100 mg BILR 355 BS

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BILR 355 BS, D1
* Drug: BILR 355 BS, D2
* Drug: BILR 355 BS, D3
* Drug: BILR 355 BS, D4
* Drug: BILR 355 BS, D5
* Drug: BILR 355 BS, D6
* Drug: BILR 355 BS, D7
* Drug: BILR 355 BS, D8
* Drug: BILR 355 BS, D10
* Drug: Placebo
* Other: high-fat breakfast
* Drug: Ritonavir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All participants in the study should be healthy males Age range from 21 to 50 years Body mass index (BMI) be within 18.5 to 29.9 kg/m2 In accordance with Good Clinical Practice and the local legislation all volunteers will have given their written informed consent prior to admission to the study Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within four weeks prior to administration or during the trial) Any laboratory value outside the clinically accepted reference range Excessive physical activities within the last week before the trial or during the trial Following exclusion criteria are of special interest for this study: Erythema, exanthema and comparable skin alterations

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D1<br> | Drug: BILR 355 BS, D1<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D2<br> | Drug: BILR 355 BS, D2<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D3<br> | Drug: BILR 355 BS, D3<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D4<br> | Drug: BILR 355 BS, D4<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D5<br> | Drug: BILR 355 BS, D5<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D6<br> | Drug: BILR 355 BS, D6<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D7<br> | Drug: BILR 355 BS, D7<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D8<br> | Drug: BILR 355 BS, D8<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: D10<br> | Drug: BILR 355 BS, D10<br> <br> Other: high-fat breakfast<br> <br> Drug: Ritonavir<br> <br> |
| Placebo Comparator: Placebo<br>for D3 - D10 | Drug: Placebo<br> <br> Drug: Ritonavir<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration of the analyte in plasma (Cmax) |  | up to 120 hours after drug administration | 
| Time to reach Cmax (tmax) |  | up to 120 hours after drug administration | 
| Area under the concentration-time curve (AUC) |  | up to 120 hours after drug administration | 
| Terminal half-life of the analyte in plasma (t1/2) |  | up to 120 hours after drug administration | 
| Total clearance of the analyte in plasma (CL/F) |  | up to 120 hours after drug administration | 
| Total mean residence time (MRTtot) |  | up to 120 hours after drug administration | 
| Apparent volume of distribution (Vz/F) |  | up to 120 hours after drug administration | 
| Renal clearance (CLR) |  | up to 72 hours after drug administration | 
| Urinary excretion (Ae) |  | up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | up to 26 days |