Effects of Single-dose and Steady-state TPV/r on the Steady-state Pharmacokinetics of Clarithromycin and a Preliminary Assessment of the Effects of a Standard High-fat Test Meal on the Steady-state Pharmacokinetics of Tipranavir

A Single-centre Open-label Study in Healthy Adult Volunteers to Determine the Effects of Single-dose and Steady-state TPV/r (500 mg/200 mg) on the Steady-state Pharmacokinetics of Clarithromycin (BIAXIN®) 500 mg Bid and a Preliminary Assessment of the Effects of a Standard High-fat Test Meal on the Steady-state Pharmacokinetics of Tipranavir

To determine the effects of single-dose and steady-state Tipranavir/Ritonavir (TPV/r) at 500 mg/200 mg bid on the steady-state pharmacokinetics of clarithromycin and to determine the effects of a standard high-fat test meal on the steady-state pharmacokinetics of tipranavir.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tipranavir; Drug: Ritonavir; Drug: Clarithromycin; Other: High-Fat Test Meal

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 capsules without difficulty
• Ability to ingest a standard high-fat test meal
• Acceptable laboratory values that indicated adequate baseline organ function were required at the time of screening. Laboratory values were considered to be acceptable if severity was less than or equal to Grade 1, based on the AIDS Clinical Trials Group (ACTG) Grading Scale
• Acceptable medical history, physical examination and 12-lead ECG were required prior to entering the treatment phase of the study
• Willingness to abstain from alcohol for 48 hours prior to study Day 0 and abstain from alcohol for the duration of the study. In addition, ingestion of red wine is not allowed within 5 days prior to Day 0 (Visit 2)
• Willingness to abstain from grapefruit or grapefruit juice or products containing grapefruit juice starting 10 days prior to any administration of study drug up until the end of the study
• Willingness to abstain from ingestion of Seville oranges, garlic supplements, St. John's Wort, or Milk Thistle, within 5 days of treatment and for the duration of the study
• Willingness to abstain from methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks, chocolate, etc.) within 48 hours of each pharmacokinetic sampling day and until after the last sample from each of the intensive sampling days was collected
• Willingness to abstain from over the counter herbal medications for the duration of the study
• Willingness to abstain from vigorous physical exercise during intensive pharmacokinetic days
• Reasonable probability for completion of the study
• Non-smokers for at least 3 months prior to Day 0

Exclusion Criteria:

• Female subjects who are of reproductive potential and who:

  1. Have positive serum β-hCG at Visit 1, or on Day 0
  2. Are not using a barrier contraceptive method for at least 3 months prior to Visit 2 (Day 0)
  3. Are not willing to use a reliable method of barrier contraception (such as diaphragm or condoms), during the trial and for 30 days after trial completion/termination
  4. Are breast-feeding
• Use of any pharmacological contraceptive (including oral, patch or injectable contraceptives) within 1 month prior to study initiation and for the duration of the study
• Use of hormone replacement therapy within 1 month prior to study initiation and for the duration of the study
• Participation in another trial with an investigational medicine within 60 days prior to Day 0 (Visit 2)
• Use of any prohibited medication listed in the protocol within 30 days prior to Day 0 (Visit 2)
• Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the trial
• History of acute illness within 60 days of trial initiation. Subjects are excluded for these disorders greater than 60 days if, in the opinion of the investigator, the subject does not qualify as a healthy volunteer
• Serological evidence of hepatitis B (HBV) or hepatitis C (HCV)
• Serological evidence of exposure to HIV
• Recent history of alcohol or substance abuse (within 6 months of study period)
• Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial
• Subjects with a seated systolic blood pressure either <100 mm Hg or >150 mm Hg
• 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 (TPV), ritonavir (RTV) or clarithromycin (CLR) to the subject
• Subjects who have taken, within 7 days prior to Day 0 (Visit 2), any over-the-counter or prescription drugs that, in the opinion of the investigator in consultation with the BI clinical monitor, might interfere with either the absorption, distribution or metabolism of the test substances
• Known hypersensitivity to TPV, RTV, sulfonamides, or CLR
• Lactose intolerance or intolerance to high-fat foods
• Allergies or intolerance to foods such as soybean, wheat, milk, eggs or gluten
• Inability to adhere to requirements of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential administration	Drug: Tipranavir; Drug: Ritonavir; Drug: Clarithromycin; Other: High-Fat Test Meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under plasma concentration time curve from 0-12 hours (AUC0-12h)	up to 12 hours
Maximum plasma concentration (Cmax)	up to 12 hours
Plasma trough concentration (Cp12h)	up to 12 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Oral clearance (CL/F)	up to 12 hours
Volume of distribution (V)	up to 12 hours
Apparent terminal half life (t1/2)	up to 12 hours
Time of maximum concentration (Tmax)	up to 12 hours
Mean Residency Time (MRT)	up to 12 hours
Number of patients with adverse events	up to day 13
Number of patients with clinically significant laboratory findings	up to day 13

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): September 1, 2003

Study Registration Dates

• First Submitted: September 25, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 29, 2014

Study Record Updates

• Last Update Posted (Estimate): September 29, 2014
• Last Update Submitted That Met QC Criteria: September 25, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Tipranavir; Clarithromycin
• Other Study ID Numbers: 1182.11