Pharmacokinetic Interaction Between Tipranavir and BILR 355 BS Plus Ritonavir in Healthy Male Volunteers

Study of Pharmacokinetic Interaction Between Tipranavir and BILR 355 BS Plus Ritonavir

To determine the effect of BILR 355/r on tipranavir/r pharmacokinetics and the effect of tipranavir/r on BILR 355 BS pharmacokinetics

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tipranavir; Drug: BILR 355 BS; Drug: High dose of ritonavir; Drug: Low dose of ritonavir

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 59 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age ≥19 and <60 years
• BMI ≥18.5 and BMI ≤29.9 kg/m2
• Ability to give signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and the local regulations

Exclusion Criteria:

• Current (symptomatic within the last 30 days) and medically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• Currently active (symptomatic within the last 30 days) diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (>24 hours) within one month prior to administration of study drug or during the trial (review with clinical monitor if questionable)
• Use of drugs within 10 days prior to administration or during the trial, which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation (review with clinical monitor if questionable)
• Participation in another trial with an investigational drug within one month prior to administration or during the trial
• Current smoker or smoked within the past 30 days
• Alcohol (more than 60 g/day) or drug abuse (positive urine test for illicit prescription or non-prescription drugs or drugs of abuse)
• Recent blood donation (more than 100 mL within 56 days prior to administration or during the trial)
• Excessive physical activities (within 1 week prior to study drug administration or during the trial)
• Any laboratory value outside the normal reference range that is of clinical relevance at screening, according to the judgment of the investigator
• Inability to comply with dietary regimen required by the protocol
• Chronic or relevant acute infections
• Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, or hepatitis C antibody positive)
• HIV-1 infected as defined by a positive HIV ELISA test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tipranavir and high dose of ritonavir plus BILR 355 BS	Drug: Tipranavir; Drug: BILR 355 BS; Drug: High dose of ritonavir
EXPERIMENTAL: BILR 355 BS with low dose of ritonavir	Drug: BILR 355 BS; Drug: Low dose of ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of tipranavir and BILR 355 BS in plasma over one dosing interval (12 hours) at steady state (AUC0-12h,ss)	up to 18 days after start of treatment
Maximum measured concentration of tipranavir and BILR 355 BS in plasma at steady state over a dosing interval τ (Cmax,ss)	up to 18 days after start of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Up to 7 weeks
Apparent clearance of BILR 355 BS, tipranavir and ritonavir in plasma following extravascular administration at steady state (CL/F,ss)	up to 18 days after start of treatment
Time from dosing to the maximum concentration of BILR 355 BS, tipranavir and ritonavir in plasma at steady state (tmax,ss)	up to 18 days after start of treatment
Terminal half-life of BILR 355 BS, tipranavir and ritonavir in plasma at steady state (t1/2,ss)	up to 18 days after start of treatment
Apparent volume of distribution of BILR 355 BS, tipranavir and ritonavir during the terminal phase λz at steady state following an extravascular dose (Vz/F,ss)	up to 18 days after start of treatment
Area under the concentration-time curve of ritonavir in plasma over one dosing interval (12 hours), (AUC0-12h)	up to 18 days after start of treatment
Maximum measured concentration of ritonavir in plasma at steady state over a dosing interval τ (Cmax,ss)	up to 18 days after start of treatment
Measured concentration of BILR 355 BS, tipranavir and ritonavir in plasma 12 hours post last dose at steady state (Cp12h,ss)	up to 18 days after start of treatment
Number of participants with clinically relevant changes in laboratory parameters	up to 28 days after start of treatment
Number of participants with clinically relevant changes in vital signs (blood pressure, pulse rate)	up to 28 days after start of treatment
Number of participants with clinically relevant changes in 12-lead ECG	up to 14 days after start of treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (ACTUAL): May 1, 2005

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (ESTIMATE): October 6, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): October 6, 2014
• Last Update Submitted That Met QC Criteria: October 2, 2014
• Last Verified: October 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; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Tipranavir
• Other Study ID Numbers: 1188.7