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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: BILR 355 BS; Other: Grapefruit juice; Drug: Nelfinavir; Drug: Atazanavir; Drug: Ritonavir

• Registration Number: NCT02257008
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2003-03
• Primary Completion: 2003-12
• Status Verified: 2014-10
• Study First Submitted: 2014-10-02
• Study First Submitted QC: 2014-10-02
• Last Update Submitted: 2014-10-02
• Study First Posted: 2014-10-06
• Last Update Posted: 2014-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 44

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single rising dose of BILR 355 BS with nelfinavir	BILR 355 BS	-
Single dose of BILR 355 BS with atazanavir	BILR 355 BS	-
Single rising dose of BILR 355 BS with grapefruit juice	Grapefruit juice	-
Single dose of BILR 355 BS with atazanavir, ritonavir	BILR 355 BS	-
Single rising dose of BILR 355 BS with grapefruit juice	BILR 355 BS	-
Single rising dose of BILR 355 BS with nelfinavir	Nelfinavir	-
Single dose of BILR 355 BS with atazanavir, ritonavir	Atazanavir	-
Single dose of BILR 355 BS with atazanavir	Atazanavir	-
Single dose of BILR 355 BS with atazanavir, ritonavir	Ritonavir	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	up to 10 days after start of treatment	Assessment of central nervous system function including Romberg's test, heel-to-toe straight line, and finger-nose tests