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

NCT02253797 | Completed Phase 1

• 1 other identifier: 1182.24
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (10)

• 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)

  14C-radiolabeled Tipranavir + Tipranavir

  -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration

• Plasma concentration 12 hours after dosing (Cp12h)

  14C-radiolabeled Tipranavir + Tipranavir

  -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration

• Area under plasma concentration time curve (AUC)

  14C-radiolabeled Tipranavir + Tipranavir

  -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration

• Time of maximum concentration (Tmax)

  14C-radiolabeled Tipranavir + Tipranavir

  -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)

  14C-radiolabeled Tipranavir + Tipranavir

  -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration

• Cumulative amount of 14C- radioactivity in Urine and feces

  up to 15 days

• Percent excretion in urine and feces

  relative to total radioactivity administered

  up to 15 days

• Time needed to achieve steady-state as determined by tipranavir trough concentrations

  up to 15 days

Secondary Outcomes (3)

• 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

Study Arms (1)

TPV/r followed by 14C-radiolabeled TPV

EXPERIMENTAL

Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir

Drug: 14C-Tipranavir; Drug: Tipranavir; Drug: Ritonavir

Interventions

14C-Tipranavir DRUG

TPV/r followed by 14C-radiolabeled TPV

Tipranavir DRUG

TPV/r followed by 14C-radiolabeled TPV

Ritonavir DRUG

TPV/r followed by 14C-radiolabeled TPV

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy HIV-negative male subjects as determined by results of screening. Healthiness was determined by medical history, laboratory testing and 12-lead ECG
• Signed written informed consent in accordance with Good Clinical Practice (GCP)
• Age \>18 and \<=60 years
• Subjects within 20% of the normal height: weight range defined by the Metropolitan Life Insurance Company Tables
• Ability to swallow numerous large capsules
• 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

You may not qualify if:

• Any finding of the medical examination (including blood pressure, pulse rate, and ECG) deviating from normal and of clinical relevance
• History of clinically significant disease including metabolic, endocrinologic, immunological, hepatic, renal, gastrointestinal, respiratory, cardiovascular, psychiatric or neurological
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator and/or the sponsor
• Subjects with a history of drug abuse or alcoholism
• Chronic or relevant acute (within 2 weeks of screening) infections
• Subjects who have taken prescription medications, over-the-counter drugs, or herbal preparations within 2 weeks of the start of the trial
• Participation in another trial with an investigational drug (in the 30 days prior to screening)
• Blood donation \>400 mL (within 1 month prior to treatment administration or during the trial)
• Any laboratory value that represents a Division of DAIDS (DAIDS) toxicity Grade \>1
• Positive urine drug screen, positive HIV antibody, positive Hepatitis C Ribonucleic acid (RNA), or positive Hepatitis B surface antigen
• History of any familial bleeding disorder

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: October 1, 2014
• Study Start: July 1, 2003
• Primary Completion: July 1, 2003
• Last Updated: October 1, 2014

Record last verified: 2014-09