Pharmacokinetics of Tipranavir/Ritonavir and Its Metabolites in Healthy Male Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: 14C-Tipranavir; Drug: Tipranavir; Drug: Ritonavir

• Registration Number: NCT02253797
• Lead Sponsor: Boehringer Ingelheim

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

Detailed Description

Not available

Study Timeline

• Study Start: 2003-07
• Primary Completion: 2003-07
• Status Verified: 2014-09
• Study First Submitted: 2014-09-25
• Study First Submitted QC: 2014-09-29
• Last Update Submitted: 2014-09-29
• Study First Posted: 2014-10-01
• Last Update Posted: 2014-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TPV/r followed by 14C-radiolabeled TPV	14C-Tipranavir	Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir
TPV/r followed by 14C-radiolabeled TPV	Ritonavir	Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir
TPV/r followed by 14C-radiolabeled TPV	Tipranavir	Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir

Primary Outcome Measures

Name	Time	Method
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
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
Percent excretion in urine and feces	up to 15 days	relative to total radioactivity administered
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
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
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
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
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
Cumulative amount of 14C- radioactivity in Urine and feces	up to 15 days
Time needed to achieve steady-state as determined by tipranavir trough concentrations	up to 15 days

Secondary Outcome Measures

Name	Time	Method
Number of subjects with adverse events	up to 15 days
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