Effect of Different Boosting Agents on Pharmacokinetics of BILR 355 BS Dissolved in Polyethylene Glycol 400 (PEG 400) in Healthy Male Volunteers

An Open Study to Investigate the Effect of Different Boosting Agents on Pharmacokinetics of Single Doses of BILR 355 BS (Dose Steps: 5 and 12.5 mg) Dissolved in 5 mL PEG 400 After Oral Administration in Healthy Male Volunteers

Assessment of the effect of different boosting agents on pharmacokinetics of a single dose of BILR 355 BS dissolved in PEG 400

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritonavir; Drug: BILR 355 BS; Other: Grapefruit juice; Drug: Nelfinavir; Drug: Atazanavir

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• All participants in the study were to be healthy males, range from 21 to 50 years of age and their body mass index (BMI) be within 18.5 to 29.9 kg/m2 (BMI calculation: weight in kilograms divided by the square of height in meters)
• In accordance with good clinical practice (GCP) and the local legislation all volunteers had to give their written informed consent prior to admission to the study

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• 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 at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study
• Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study
• Participation in another trial with an investigational drug (<= two months prior to administration or during the trial)
• Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation (>= 100 mL within four weeks prior to administration or during the trial)
• Any laboratory value outside the clinically accepted reference range
• Excessive physical activities within the last week before the trial or during the trial

Following exclusion criteria are of special interest for this study:

• Erythema, exanthema and comparable skin alterations
• For the boosting agents atazanavir and atazanavir plus ritonavir, subjects with a PQ interval length in the screening ECG of > 200 ms or any higher degree of atrio-ventricular (AV) block were to be excluded

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single rising dose of BILR 355 BS with grapefruit juice	Drug: BILR 355 BS; Other: Grapefruit juice
Experimental: Single rising dose of BILR 355 BS with nelfinavir	Drug: BILR 355 BS; Drug: Nelfinavir
Experimental: Single dose of BILR 355 BS with atazanavir	Drug: BILR 355 BS; Drug: Atazanavir
Experimental: Single dose of BILR 355 BS with atazanavir, ritonavir	Drug: Ritonavir; Drug: BILR 355 BS; Drug: Atazanavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration of the analyte in the plasma (Cmax)	up to 120 hours after start of treatment
Time from dosing to the maximum concentration of the analyte in plasma (tmax)	up to 120 hours after start of treatment
Area under the concentration-time curve of the analyte in plasma at different time points (AUC)	up to 120 hours after start of treatment
Apparent terminal half-life of the analyte in plasma (t1/2)	up to 120 hours after start of treatment
Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/F)	up to 120 hours after start of treatment
Total mean residence time of the analyte in the body (MRTtot)	up to 120 hours after start of treatment
Apparent volume of distribution of the analyte during the terminal phase λz following extravascular administration (Vz/F)	up to 120 hours after start of treatment
Renal clearance of the analyte determined over the dosing interval τ (CLR)	up to 120 hours after start of treatment
Amount of the analyte excreted into urine (Ae)	up to 72 hours after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with clinically relevant changes in laboratory parameters		up to 10 days after start of treatment
Number of participants with clinically relevant changes in vital signs (blood pressure, pulse-, respiratory rate, body temperature)		up to 10 days after start of treatment
Number of participants with clinically relevant changes in 12-lead ECG		up to 10 days after start of treatment
Number of participants with clinically relevant changes in faecal occult blood testing		up to 10 days after start of treatment
Number of participants with adverse events		Up to 25 days
Global tolerability assessment by investigator on a 5-point scale		Up to 10 days after start of treatment
Number of participants with clinically relevant changes in neurological assessment	Assessment of central nervous system function including Romberg's test, heel-to-toe straight line, and finger-nose tests	up to 10 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: March 1, 2003
• Primary Completion (Actual): December 1, 2003

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; Nelfinavir; Atazanavir Sulfate
• Other Study ID Numbers: 1188.6