Effects of Steady-state TPV/RTV on the Single-dose Pharmacokinetics of Rifabutin and the Effects of Single-dose Rifabutin on the Steady-state Pharmacokinetics of TPV in Healthy Adult Volunteers

NCT02251171 | Completed Phase 1

• 1 other identifier: 1182.44
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to determine the effects of steady-state Tipranavir (TPV) / Ritonavir (RTV) (500mg/200mg bid) on the single-dose pharmacokinetics of Rifabutin (RFB) and to determine the effects of single-dose RFB on the steady-state pharmacokinetics of TPV 500mg (co-administered with RTV 200mg)

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration of the analytes in plasma (Cmax)

  up to 144 hours after drug administration

• Drug concentration of the analytes in plasma at 12 hours after administration (Cp12h)

  up to 12 hours after drug administration

• Area under plasma concentration time curve from 0-12 hours (AUC0-12h)

  up to 12 hours after drug administration

• Area under the plasma drug concentration-time curve from time zero to infinity of the analytes (AUC0-∞)

  up to 144 hours after drug administration

Secondary Outcomes (6)

• Oral clearance (CL/F)

  up to 144 hours after drug administration

• Time of maximum concentration (Tmax)

  up to 144 hours after drug administration

• Volume of distribution (V)

  up to 144 hours after drug administration

• Apparent terminal half life (t1/2)

  up to 144 hours after drug administration

• Number of subjects with adverse events

  up to 24 days

Study Arms (1)

TPV/RTV - Rifabutin

EXPERIMENTAL

Day 1: single dose Rifabutin Days 8-20: morning and evening doses of Tipranavir/Ritonavir Day 15: single dose Rifabutin

Drug: Tipranavir; Drug: Ritonavir; Drug: Rifabutin

Interventions

Tipranavir DRUG

TPV/RTV - Rifabutin

Ritonavir DRUG

Also known as: Norvir-SEC®

TPV/RTV - Rifabutin

Rifabutin DRUG

Also known as: Mycobutin®

TPV/RTV - Rifabutin

Eligibility Criteria

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

You may qualify if:

• Male and female subjects between 18 and 60 years of age inclusive
• A Body Mass Index (BMI) between 18 and 29 kg/m2
• Signed informed consent prior to trial participation
• Ability to swallow multiple large capsules without difficulty
• Acceptable laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity was less than or equal to Grade 1, based on the AIDS Clinical Trials Group (ACTG) Grading Scale. All abnormal laboratory values greater than Grade 1 are subject to approval by the trial clinical monitor
• Acceptable medical history, physical examination, and 12-lead ECG are required prior to entering the treatment phase of the study. The requirement for chest X-ray is left to the investigator's discretion
• Willingness to abstain from the following starting 14 days prior to any administration of study drug up until the end of the study:
• Grapefruit or grapefruit juice
• Red wine
• Seville oranges
• St. John's Wort or Milk Thistle
• Willingness to abstain from alcohol starting 2 days prior to administration of any study drug up to the end of the study
• Willingness to abstain from the following within 72 hours of pharmacokinetic (PK) sampling:
• Garlic supplements
• Methylxanthine containing drinks (coffee, tea, cola, energy drinks, chocolate, etc.)

You may not qualify if:

• As a guideline, subjects who have abnormal laboratory values at screening, and who are taking prescription medications are excluded:
• Female subjects with reproductive potential who:
• Have positive serum β-human chorionic gonadotropin at Visit 1, or on study Day 0 or study Day 1
• Have not been using a barrier contraceptive method for at least 3 months prior to Visit 3 (study Day 1)
• Are not willing to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during the trial and 60 days after completion/termination
• Are breast-feeding
• Participation in another trial with an investigational medicine within 60 days prior to study Day 0 (Visit 2)
• Use of any medication listed in Protocol within 30 days prior to study Day 0 (Visit 2)
• Use of any pharmacological contraceptive (including oral, patch or injectable contraceptives) within 1 month prior to study Day 0 and for the duration of the study. Use of Depo-Provera is excluded for six months prior to study Day 0
• Use of hormone replacement therapy within 1 month prior to study Day 0 and for the duration of the study
• Administration of antibiotics within 10 days prior to study Day 0 (Visit 2) or during the trial
• History of acute illness within sixty (60) days of study Day 0. Subjects are excluded if they have an acute illness greater than sixty days prior to study Day 0 if, in the opinion of the investigator, the subject did not qualify as a healthy volunteer
• History of thrombotic disease
• History of migraine headache
• Have serological evidence of hepatitis B or C virus

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Rifabutin

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: September 29, 2014
• Study Start: August 1, 2003
• Primary Completion: October 1, 2003
• Last Updated: September 29, 2014

Record last verified: 2014-09