Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir (TPV/r) With Single-dose Valaciclovir (VAL) in Healthy Volunteers

Study Overview
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Brief Summary
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Assessment of the interaction of tipranavir/ritonavir (TPV/RTV) and valaciclovir (VAL), a prodrug of aciclovir (ACV)

Official Title
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An Open-label One-sequence Cross-over Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir 500/200 mg With Single-dose Valaciclovir (500 mg) in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tipranavir
* Drug: Ritonavir
* Drug: Valaciclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and non-pregnant, non-lactating female subjects as determined by results of screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and willingness to comply with all study requirements Age >19 and <59 years (20 - 58 years inclusive) Weight ≥ 60 kg Body mass index (BMI) >18.5 and <29.9 kg/m2 Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Atrioventricular (AV) block including 1° Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, oncological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Relevant 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 Known hypersensitivity to TPV, RTV, valaciclovir, aciclovir or antiretroviral drugs (marketed or experimental use as part of clinical research studies) Known elevated liver enzymes in past trials with any compound Intake of drugs with a long half-life (>24 hours) (<1 month prior to administration) Prescription or over the counter medications (including vitamins, minerals, herbal supplements and antacids), dietary supplements 14 days prior to study drug administration or expected during the trial) Participation in another trial with an investigational drug (<2 months prior to administration or expected during trial) Smoker with a consumption of >10 cigarettes or >3 cigars or >3 pipes/day and those who cannot keep tobacco intake constant Alcohol (>40 g/day for males and >20 g/day for females) and drug abuse Blood donation or loss >400 mL, < 3 month prior to administration Clinically relevant laboratory abnormalities Transaminases above reference values in the history Inability to comply with dietary regimen of study centre For female subjects: Pregnancy or planning to become pregnant within 60 days of study completion Positive pregnancy test Have not been using a barrier method of contraception for at least 3 months prior to participation in the study if of childbearing potential and not surgically sterilized Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial if of childbearing potential and not surgically sterilized Chronic use of oral contraception or hormone replacement containing ethinyl estradiol Breast-feeding

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 58 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
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPV/r with valaciclovir<br>VAL 2 days (on days 1 and 13), TPV/r 12 days (on days 2 to 13) | Drug: Tipranavir<br> <br> Drug: Ritonavir<br> <br> Drug: Valaciclovir<br> <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 aciclovir in plasma over the time interval t0h to t12h (AUC0-12) |  | up to 12 hours after drug administration | 
| Maximum measured concentration of aciclovir in plasma (Cmax) |  | up to 12 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-12 for Tipranavir (TPV) |  | up to 12 hours after drug administration | 
| Cmax for TPV |  | up to 12 hours after drug administration | 
| Drug concentration of TPV in plasma at 12 hours after administration (C12h) |  | up to 12 hours after drug administration | 
| Apparent clearance of the analyte in the plasma after extravascular administration (CL/F) |  | up to 12 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) |  | up to 12 hours after drug administration | 
| Terminal half-life of the analyte in plasma (t1/2) |  | up to 12 hours after drug administration | 
| Number of subjects with adverse events |  | up to 14 days after last drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | up to 14 days after last drug administration | 
| AUC0-12 for Ritonavir (RTV) |  | up to 12 hours after drug administration | 
| Cmax for RTV |  | up to 12 hours after drug administration | 
| Drug concentration of RTV in plasma at 12 hours after administration (C12h) |  | up to 12 hours after drug administration |