Bioavailability of Tipranavir/Ritonavir Paediatric Solution Compared to Tipranavir/Ritonavir Capsules in Healthy Female and Male Subjects

Study Overview
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Brief Summary
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Study to determine the relative bioavailability of 500/200 mg of tipranavir/ritonavir (TPV/r) oral solution compared to 500/200 mg of TPV/r capsules following oral administration and to investigate the relative bioavailability of 500/200 mg of TPV/r oral solution with food versus without food.

Official Title
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Relative Bioavailability of 500/200 mg of Tipranavir/Ritonavir Paediatric Solution Compared to 500/200 mg of Tipranavir/Ritonavir Capsules Following Oral Administration and Bioavailability of 500/200 mg Tipranavir/Ritonavir Paediatric Solution Under the Influence of Food in Healthy Female and Male Subjects. An Open-label, Randomised, Single-dose, Three-way Crossover Trial.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tipranavir oral solution
* Drug: Tipranavir capsules
* Drug: Ritonavir oral solution
* Drug: Ritonavir soft gel capsules
* Other: High fat breakfast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, HR), 12-lead ECG, clinical laboratory tests No finding deviating from normal and of clinical relevance No evidence of a clinically relevant concomitant disease Age ≥ 18 and Age ≤ 55 years 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: 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 at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial (e.g. drugs which contain polyethylene glycol or vitamin E) Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes/day or 3 cigars/day or 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) Drug abuse Veins unsuited for iv puncture on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) Blood donation (more than 100 mL within four weeks prior to administration or during the trial) History of any bleeding disorder or acute blood coagulation defect of vitamin K deficiency caused by anticoagulation therapy or malabsorption Vitamin E supplement intake Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre For female subjects: Pregnancy Positive pregnancy test No adequate contraception e.g. oral contraceptives, sterilization, intrauterine device Inability to maintain this adequate contraception during the whole study period Lactation period

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPV/r with food<br>Tipranavir/Ritonavir paediatric/oral solution | Drug: Tipranavir oral solution<br> <br> Drug: Ritonavir oral solution<br> <br> Other: High fat breakfast<br> <br> |
| Experimental: TPV/r<br>Tipranavir/Ritonavir paediatric/oral solution | Drug: Tipranavir oral solution<br> <br> Drug: Ritonavir oral solution<br> <br> |
| Active Comparator: TPV/r capsules<br> | Drug: Tipranavir capsules<br> <br> Drug: Ritonavir soft gel capsules<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration time curve of tipranavir in plasma over the time interval from 0 extrapolated to infinity) |  | up to 72 hours after drug administration | 
| Cmax (maximum concentration of tipranavir in plasma) |  | up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (area under the concentration-time curve of tipranavir in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 72 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of tipranavir in plasma) |  | up to 72 hours after drug administration | 
| t1/2 (terminal half-life of tipranavir in plasma) |  | up to 72 hours after drug administration | 
| MRTpo (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours after drug administration | 
| CLpo/F (apparent clearance of tipranavir in the plasma after extravascular administration) |  | up to 72 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 72 hours after drug administration | 
| Number of subjects with adverse events |  | up to day 18 |