Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of BILR 355 BS Plus Low Dose Ritonavir in HIV-uninfected Male Volunteers

Study Overview
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Brief Summary
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Study to determine the safety, tolerability and pharmacokinetics of BILR 355 BS plus low dose ritonavir in healthy male volunteers.

Official Title
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An Investigator Blinded, Randomized, Placebo-controlled Multiple Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of BILR 355 BS Plus Low Dose Ritonavir in HIV-uninfected Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BILR 355 BS, solution
* Drug: BILR 355 BS, tablet
* Drug: Ritonavir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males who meet the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests No finding deviating from normal (except as noted below) and of clinical relevance No evidence of a clinically relevant concomitant disease Age ≥18 years and <60 BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Exclusion Criteria: Current and medically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of 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 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 one month prior to administration of study drug or during the trial Use of drugs within 10 days prior to administration or during the trial, which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation Participation in another trial with an investigational drug within one month prior to administration or during the trial Smoker Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) Drug abuse Recent blood donation (more than 100 mL within 4 weeks prior to administration or during the trial) Excessive physical activities (within 1 week prior to administration or during the trial) Any laboratory value outside the normal reference range that is of clinical relevance Inability to comply with dietary regimen of study centre Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody positive) HIV-1 infected as defined by a positive HIV ELISA test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BILR 355 BS, solution<br>escalating doses | Drug: BILR 355 BS, solution<br> <br> Drug: Ritonavir<br> <br> |
| Experimental: BILR 355 BS, tablet<br>escalating doses | Drug: BILR 355 BS, tablet<br> <br> Drug: Ritonavir<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ (area under the concentration time curve of BILR 355 in plasma over one dosing interval at steady state) |  | up to day 11 | 
| Cmax (maximum concentration of BILR 355 in plasma) |  | up to day 11 | 
| Time for BILR 355 BS to achieve steady state |  | up to day 11 | 
| Cmin,ss (trough concentration of BILR 355 BS in plasma at steady state) |  | up to day 11 | 
| Incidence of dose limiting toxicity |  | up to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax (time from dosing to the maximum concentration of BILR 355 in plasma) |  | up to day 11 | 
| AUCτ (area under the concentration time curve of metabolite 402 in plasma over one dosing interval at steady state) |  | up to day 11 | 
| Cmax (maximum concentration of metabolite 402 in plasma) |  | up to day 11 | 
| Ae (amount of BILR 355 excreted in the urine over the time interval from 0 to the time of the last urine collection interval) |  | up to day 11 | 
| Metabolite BILR 402 Ae (amount of BILR 402 excreted in the urine over the time interval from 0 to the time of the last urine collection interval) |  | up to day 11 | 
| Number of subjects with adverse events |  | up to 42 days |