Healthy
Conditions
Brief summary
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
Interventions
DRUGTadalafil
administered days 1, 8 and 16
DRUGTipranavir
administered days 8-18
DRUGRitonavir
administered days 8-18
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed informed consent 2. Healthy male subjects aged between 18 years and 55 years inclusive 3. Weighing at least 40 kg 4. Volunteers must be hospitalized on day of pharmacokinetic assessments for each regimen 5. Volunteers must be willing to complete all study-related activities 6. Each volunteer must have a valid social security regimen 7. Each volunteer must have acceptable medical history, physical examination and laboratory test 8. Volunteers with negative HIV serology
Exclusion criteria
1. 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) 2. Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, haematological, oncological or hormonal disorders 4. Known elevated liver enzymes in past clinical trials with any compound (experimental or marketed) 5. Clinically relevant laboratory abnormalities and all abnormal laboratory values \>Grade 1, based on the Division of AIDS Grading Scale 6. 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 7. Volunteers who are using any form of organic nitrate, either regularly and/or intermittently (contraindication to use tadalafil) 8. Hypersensitivity to tadalafil, tipranavir, ritonavir or their excipients 9. Concurrent treatment with other experimental compounds 10. Inadequate venous access 11. 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) 12. Clinically unacceptable result at the screening physical examination 13. Use of investigational medications within 30 days before study entry 14. Patients hospitalized in a medical or social establishment, for any other reason than research 15. People deprived of judicial or administrative freedom.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Elimination half-life (t1/2) | up to 72 hours after drug administration |
| Total body clearance (Cl/F) | up to 72 hours after drug administration |
| Cmax for Tipranavir and Ritonavir | up to 12 hours after drug administration |
| Number of subjects with adverse events | up to 42 days |
| Volume of distribution, | up to 72 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 |
Outcome results
None listed