Healthy
Conditions
Brief summary
Study to evaluate the pharmacokinetics of Tipranavir and its metabolites including excretion and mass balance of parent compound and radioactivity at steady-state; to isolate, identify and quantify major metabolites of tipranavir in plasma, urine and feces
Interventions
DRUG14C-Tipranavir
DRUGTipranavir
DRUGRitonavir
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy HIV-negative male subjects as determined by results of screening. Healthiness was determined by medical history, laboratory testing and 12-lead ECG 2. Signed written informed consent in accordance with Good Clinical Practice (GCP) 3. Age \>18 and \<=60 years 4. Subjects within 20% of the normal height: weight range defined by the Metropolitan Life Insurance Company Tables 5. Ability to swallow numerous large capsules 6. Willingness to abstain from smoking, ingesting methylxanthine containing drinks or food (coffee, tea, cola, chocolate, etc.), or ingesting alcohol, St. John's Wort, milk thistle, garlic supplements, Seville oranges, and grapefruit or grapefruit juice for the duration of the study
Exclusion criteria
1. Any finding of the medical examination (including blood pressure, pulse rate, and ECG) deviating from normal and of clinical relevance 2. History of clinically significant disease including metabolic, endocrinologic, immunological, hepatic, renal, gastrointestinal, respiratory, cardiovascular, psychiatric or neurological 3. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator and/or the sponsor 4. Subjects with a history of drug abuse or alcoholism 5. Chronic or relevant acute (within 2 weeks of screening) infections 6. Subjects who have taken prescription medications, over-the-counter drugs, or herbal preparations within 2 weeks of the start of the trial 7. Participation in another trial with an investigational drug (in the 30 days prior to screening) 8. Blood donation \>400 mL (within 1 month prior to treatment administration or during the trial) 9. Any laboratory value that represents a Division of DAIDS (DAIDS) toxicity Grade \>1 10. Positive urine drug screen, positive HIV antibody, positive Hepatitis C Ribonucleic acid (RNA), or positive Hepatitis B surface antigen 11. History of any familial bleeding disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time needed to achieve steady-state as determined by tipranavir trough concentrations | up to 15 days | — |
| Apparent terminal half life (t1/2) | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | 14C-radiolabeled Tipranavir + Tipranavir |
| Cumulative amount of 14C- radioactivity in Urine and feces | up to 15 days | — |
| Percent excretion in urine and feces | up to 15 days | relative to total radioactivity administered |
| Radioactive levels of 14C-Tipranavir in plasma and blood | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | — |
| Radioactive erythrocyte-plasma partition ratio | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | — |
| Maximum measured concentration of the analyte in plasma (Cmax) | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | 14C-radiolabeled Tipranavir + Tipranavir |
| Plasma concentration 12 hours after dosing (Cp12h) | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | 14C-radiolabeled Tipranavir + Tipranavir |
| Area under plasma concentration time curve (AUC) | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | 14C-radiolabeled Tipranavir + Tipranavir |
| Time of maximum concentration (Tmax) | -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration | 14C-radiolabeled Tipranavir + Tipranavir |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with abnormal changes in laboratory parameters | up to day 14 |
| Number of subjects with clinically significant changes in Electrocardiogram (ECG) | up to day 6 |
| Number of subjects with adverse events | up to 15 days |
Outcome results
None listed