Effect of Different Boosting Agents on Pharmacokinetics of BILR 355 BS Dissolved in Polyethylene Glycol 400 (PEG 400) in Healthy Male Volunteers

Study Overview
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Brief Summary
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Assessment of the effect of different boosting agents on pharmacokinetics of a single dose of BILR 355 BS dissolved in PEG 400

Official Title
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An Open Study to Investigate the Effect of Different Boosting Agents 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

Conditions
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Healthy

Intervention / Treatment
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* Drug: BILR 355 BS
* Other: Grapefruit juice
* Drug: Nelfinavir
* Drug: Atazanavir
* Drug: Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants in the study were to be healthy males, range from 21 to 50 years of age and their body mass index (BMI) be within 18.5 to 29.9 kg/m2 (BMI calculation: weight in kilograms divided by the square of height in meters) In accordance with good clinical practice (GCP) and the local legislation all volunteers had to give 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 For the boosting agents atazanavir and atazanavir plus ritonavir, subjects with a PQ interval length in the screening ECG of > 200 ms or any higher degree of atrio-ventricular (AV) block were to be excluded

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

Sexes Eligible for Study
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Male

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single rising dose of BILR 355 BS with grapefruit juice<br> | Drug: BILR 355 BS<br> <br> Other: Grapefruit juice<br> <br> |
| Experimental: Single rising dose of BILR 355 BS with nelfinavir<br> | Drug: BILR 355 BS<br> <br> Drug: Nelfinavir<br> <br> |
| Experimental: Single dose of BILR 355 BS with atazanavir<br> | Drug: BILR 355 BS<br> <br> Drug: Atazanavir<br> <br> |
| Experimental: Single dose of BILR 355 BS with atazanavir, ritonavir<br> | Drug: BILR 355 BS<br> <br> Drug: Atazanavir<br> <br> Drug: Ritonavir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration of the analyte in the plasma (Cmax) |  | up to 120 hours after start of treatment | 
| Time from dosing to the maximum concentration of the analyte in plasma (tmax) |  | up to 120 hours after start of treatment | 
| Area under the concentration-time curve of the analyte in plasma at different time points (AUC) |  | up to 120 hours after start of treatment | 
| Apparent terminal half-life of the analyte in plasma (t1/2) |  | up to 120 hours after start of treatment | 
| Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/F) |  | up to 120 hours after start of treatment | 
| Total mean residence time of the analyte in the body (MRTtot) |  | up to 120 hours after start of treatment | 
| Apparent volume of distribution of the analyte during the terminal phase λz following extravascular administration (Vz/F) |  | up to 120 hours after start of treatment | 
| Renal clearance of the analyte determined over the dosing interval τ (CLR) |  | up to 120 hours after start of treatment | 
| Amount of the analyte excreted into urine (Ae) |  | up to 72 hours after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinically relevant changes in laboratory parameters |  | up to 10 days after start of treatment | 
| Number of participants with clinically relevant changes in vital signs (blood pressure, pulse-, respiratory rate, body temperature) |  | up to 10 days after start of treatment | 
| Number of participants with clinically relevant changes in 12-lead ECG |  | up to 10 days after start of treatment | 
| Number of participants with clinically relevant changes in faecal occult blood testing |  | up to 10 days after start of treatment | 
| Number of participants with adverse events |  | Up to 25 days | 
| Global tolerability assessment by investigator on a 5-point scale |  | Up to 10 days after start of treatment | 
| Number of participants with clinically relevant changes in neurological assessment | Assessment of central nervous system function including Romberg's test, heel-to-toe straight line, and finger-nose tests | up to 10 days after start of treatment |