Study of Pharmacokinetic Interaction Between Combivir® (ZDV+3TC) and BILR 355 BS Plus Ritonavir in Healthy Subjects

Study of Pharmacokinetic Interaction Between Combivir® (ZDV+3TC) and BILR 355 BS Plus Ritonavir

Study to determine the effect of BILR 355/r on Combivir® pharmacokinetics and the effect of Combivir® on BILR 355 BS pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritonavir; Drug: BILR 355 BS; Drug: Combivir®

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females who meet the inclusion/exclusion criteria, females are not 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. Body Mass Index (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 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: Combivir® plus BILR 355/Ritonavir	Drug: Ritonavir; Other Names: NORVIR®; Drug: BILR 355 BS; Drug: Combivir®
Experimental: BILR 355/Ritonavir	Drug: Ritonavir; Other Names: NORVIR®; Drug: BILR 355 BS

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 at steady state (AUC0-12h,ss)	up to day 18
Maximum measured concentration of the analyte in plasma at steady state over a dosing interval τ (Cmax,ss)	up to day 18

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 day 18
Time from dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss)	up to day 18
Terminal half-life of the analyte in plasma at steady state (t1/2,ss)	up to day 18
Apparent volume of distribution during the terminal phase λz at steady state following an extravascular dose (Vz/Fss)	up to day 18
Measured concentration of the analyte in plasma 12 hours post last dose at steady state (Cp12h, ss)	up to day 18
Number of subjects with adverse events	up to 49 days
Number of subjects with abnormal laboratory parameters	up to 49 days
Number of subjects with clinically significant findings in vital signs	up to 49 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• 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; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; 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; Lamivudine, zidovudine drug combination
• Other Study ID Numbers: 1188.9