Study of Pharmacokinetic Interaction Between Kaletra® (LPV/r) and BILR 355 BS Plus Ritonavir in Healthy Subjects

Study of Pharmacokinetic Interaction Between Kaletra® (LPV/r) and BILR 355 BS Plus Ritonavir

To determine the pharmacokinetic effect of BILR 355 BS on Kaletra® and of Kaletra® on BILR 355 BS

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BILR 355 BS; Drug: Ritonavir (RTV); Drug: Kaletra®

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females who meet the inclusion/exclusion criteria; females must not be pregnant or nursing, and agree to use a double-barrier method of birth control (condoms or diaphragm plus spermicide) throughout the trial (alone or in addition to other methods of birth control such as oral contraceptives)
2. Age ≥18 and <60 years
3. BMI ≥18.5 and BMI ≤29.9 kg/m2
4. 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:

1. Current (symptomatic within the last 30 days) and medically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Surgery of gastrointestinal tract (except appendectomy)
3. Currently active (symptomatic within the last 30 days) diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
4. History of relevant orthostatic hypotension, fainting spells or blackouts
5. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
6. 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)
7. 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)
8. Participation in another trial with an investigational drug within one month prior to administration or during the trial
9. Current smoker
10. Alcohol (more than 60 g/day) or drug abuse (positive urine test for illicit prescription or non-prescription drugs or drugs of abuse)
11. Recent blood donation (more than 100 mL within 4 weeks prior to administration or during the trial)
12. Excessive physical activities (within 1 week prior to study drug administration or during the trial)
13. Any laboratory value outside the normal reference range that is of clinical relevance at screening, according to the judgment of the investigator
14. Inability to comply with dietary regimen required by the protocol
15. Chronic or relevant acute infections
16. Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, or hepatitis C antibody positive)
17. 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 Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: BILR 355 BS; Drug: Ritonavir (RTV); NORVIR®; Drug: Kaletra®; (lopinavir (LPV) and ritonavir (RTV))
Experimental: Group B	Drug: BILR 355 BS; Drug: Ritonavir (RTV); NORVIR®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analyte in plasma over one dosing interval (12 hours) at steady state (AUC0-12h,ss)	Up to 12 h after the last drug administration of BILR 355
Maximum measured concentration of the analyte in plasma at steady state over a dosing interval τ (Cmax,ss)	Up to 96 h after the last drug administration of BILR 355

Secondary Outcome Measures

Outcome Measure	Time Frame
Apparent clearance of the analyte in plasma following extravascular administration at steady state (CL/F,ss)	Up to 96 h after the last drug administration of BILR 355
Time from dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss)	Up to 96 h after the last drug administration of BILR 355
Terminal half-life of the analyte in plasma at steady state (t1/2,ss)	Up to 96 h after the last drug administration of BILR 355
Apparent volume of distribution during the terminal phase λz at steady state following an extravascular dose (Vz/F,ss)	Up to 96 h after the last drug administration of BILR 355
Area under the plasma concentration time curve (0-12 hours) (AUC0-12h) for RTV	Up to 12 h after RTV administration
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for RTV	Up to 96 h after the last drug administration of BILR 355
Measured concentration of the analyte in plasma 12 hours post last dose at steady state (Cp12h,ss)	Up to 12 h after the last drug administration of BILR 355
Number of participants with Adverse Events	Up to day 35 after first drug administration
Number of participants with abnormal changes in clinical laboratory parameters	Up to day 35 after first drug administration
Number of participants with abnormal findings in physical examination	Up to day 35 after first drug administration
Number of participants with clinically significant changes in vital signs	Up to day 35 after first drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): June 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
• Other Study ID Numbers: 1188.8