Pharmacokinetic of Tadalafil Co-administered With Tipranavir/Ritonavir to Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to assess the effects of single-dose and steady-state tipranavir/ritonavir 500 mg/200 mg on the single-dose pharmacokinetics of tadalafil 10 mg

Official Title
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Assessment of Single-dose Oral Tadalafil Pharmacokinetic Characteristics When Simultaneously Co-administered With Single-dose and Steady-state Tipranavir/Ritonavir 500 mg/200 mg to Healthy Male Volunteers

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Healthy male subjects aged between 18 years and 55 years inclusive Weighing at least 40 kg Volunteers must be hospitalized on day of pharmacokinetic assessments for each regimen Volunteers must be willing to complete all study-related activities Each volunteer must have a valid social security regimen Each volunteer must have acceptable medical history, physical examination and laboratory test Volunteers with negative HIV serology Exclusion Criteria: History or presence of allergy to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. (If heparin is used during pharmacokinetic (PK) sampling, subjects with a history of sensibility to heparin or heparin-induced thrombocytopenia should not be enrolled) Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, haematological, oncological or hormonal disorders Known elevated liver enzymes in past clinical trials with any compound (experimental or marketed) Clinically relevant laboratory abnormalities and all abnormal laboratory values >Grade 1, based on the Division of AIDS Grading Scale Subjects with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering tipranavir, ritonavir or tadalafil to the subject Volunteers who are using any form of organic nitrate, either regularly and/or intermittently (contraindication to use tadalafil) Hypersensitivity to tadalafil, tipranavir, ritonavir or their excipients Concurrent treatment with other experimental compounds Inadequate venous access Contraindications to tadalafil: Volunteers with mild or moderate hepatic impairment, Renal insufficiency or Cardiovascular disease (patients with a myocardial infarction within the last 90 days, unstable angina or angina occurring during sexual intercourse, patients with New York Heart Association Class 2 or greater heart failure in the last 6 months, patients with uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg), and patients with a stroke within the last 6 months) Clinically unacceptable result at the screening physical examination Use of investigational medications within 30 days before study entry Patients hospitalized in a medical or social establishment, for any other reason than research People deprived of judicial or administrative freedom.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential treatment<br> | Drug: Tadalafil<br>* administered days 1, 8 and 16<br>Drug: Tipranavir<br>* administered days 8-18<br>Drug: Ritonavir<br>* administered days 8-18<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for Tadalafil |  | up to 72 hours after drug administration | 
| Plasma Concentration (Cp12h) for Tadalafil |  | 12 hours after drug administration | 
| Area Under Plasma Concentration-time Curve (AUC0-72h) for Tadalafil |  | up to 72 hours after drug administration | 
| AUC0-∞ for Tadalafil |  | up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for Tipranavir and Ritonavir |  | up to 12 hours after drug administration | 
| Cp12 for Tipranavir and Ritonavir |  | 12 hours after drug administration | 
| AUC0-12hTipranavir and Ritonavir |  | 12 hours after drug administration | 
| Time of Maximum Concentration |  | up to 72 hours after drug administration | 
| Elimination half-life (t1/2) |  | up to 72 hours after drug administration | 
| Total body clearance (Cl/F) |  | up to 72 hours after drug administration | 
| Volume of distribution, |  | up to 72 hours after drug administration | 
| Number of subjects with adverse events |  | up to 42 days |