Study of Pharmacokinetic Interaction Between Kaletra® (LPV/r) and BILR 355 BS Plus Ritonavir in Healthy Subjects

Study Overview
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Brief Summary
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To determine the pharmacokinetic effect of BILR 355 BS on Kaletra® and of Kaletra® on BILR 355 BS

Official Title
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Study of Pharmacokinetic Interaction Between Kaletra® (LPV/r) and BILR 355 BS Plus Ritonavir

Conditions
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Healthy

Intervention / Treatment
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* Drug: BILR 355 BS
* Drug: Ritonavir (RTV)
* Drug: Kaletra®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females who meet the inclusion/exclusion criteria; females must not be pregnant or nursing, and agree to use a double-barrier method of birth control (condoms or diaphragm plus spermicide) throughout the trial (alone or in addition to other methods of birth control such as oral contraceptives) Age ≥18 and <60 years BMI ≥18.5 and BMI ≤29.9 kg/m2 Ability to give signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local regulations Exclusion Criteria: Current (symptomatic within the last 30 days) and medically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Currently active (symptomatic within the last 30 days) diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts 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 (review with clinical monitor if questionable) 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 (review with clinical monitor if questionable) Participation in another trial with an investigational drug within one month prior to administration or during the trial Current smoker Alcohol (more than 60 g/day) or drug abuse (positive urine test for illicit prescription or non-prescription drugs or drugs of 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 study drug administration or during the trial) Any laboratory value outside the normal reference range that is of clinical relevance at screening, according to the judgment of the investigator Inability to comply with dietary regimen required by the protocol Chronic or relevant acute infections Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, 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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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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Drug: BILR 355 BS<br> <br> Drug: Ritonavir (RTV)<br>* NORVIR®<br>Drug: Kaletra®<br>* (lopinavir (LPV) and ritonavir (RTV))<br>|
| Experimental: Group B<br> | Drug: BILR 355 BS<br> <br> Drug: Ritonavir (RTV)<br>* NORVIR®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over one dosing interval (12 hours) at steady state (AUC0-12h,ss) |  | Up to 12 h after the last drug administration of BILR 355 | 
| Maximum measured concentration of the analyte in plasma at steady state over a dosing interval τ (Cmax,ss) |  | Up to 96 h after the last drug administration of BILR 355 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/F,ss) |  | Up to 96 h after the last drug administration of BILR 355 | 
| Time from dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss) |  | Up to 96 h after the last drug administration of BILR 355 | 
| Terminal half-life of the analyte in plasma at steady state (t1/2,ss) |  | Up to 96 h after the last drug administration of BILR 355 | 
| Apparent volume of distribution during the terminal phase λz at steady state following an extravascular dose (Vz/F,ss) |  | Up to 96 h after the last drug administration of BILR 355 | 
| Area under the plasma concentration time curve (0-12 hours) (AUC0-12h) for RTV |  | Up to 12 h after RTV administration | 
| Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for RTV |  | Up to 96 h after the last drug administration of BILR 355 | 
| Measured concentration of the analyte in plasma 12 hours post last dose at steady state (Cp12h,ss) |  | Up to 12 h after the last drug administration of BILR 355 | 
| Number of participants with Adverse Events |  | Up to day 35 after first drug administration | 
| Number of participants with abnormal changes in clinical laboratory parameters |  | Up to day 35 after first drug administration | 
| Number of participants with abnormal findings in physical examination |  | Up to day 35 after first drug administration | 
| Number of participants with clinically significant changes in vital signs |  | Up to day 35 after first drug administration |