Pharmacokinetics and Safety of BILR 355 in Healthy Male Volunteers

An Open-label, Randomized, Crossover Relative BA Study of Pharmacokinetics and Safety of New SDS-containing Tablet and Capsule Formulations of BILR 355 Compared to the Current Formulation (50 mg Tablet), After Single Dose Oral Administration of BILR 355 Plus Low Dose Ritonavir in Healthy Male Volunteers

Study to determine the single dose, relative BA of new SDS-containing formulations of BILR 355 (150 mg and 200 mg capsules and 150 mg tablet), compared to the current SDS tablet formulation (50 mg tablet)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritonavir; Drug: BILR 355 - Treatment A (current tablet formulation); Drug: BILR 355 - Treatment B (new tablet formulation); Drug: BILR 355 - Treatment C (new capsule formulation); Drug: BILR 355 - Treatment D (current tablet formulation); Drug: BILR 355 - Treatment E (new capsule formulation)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy HIV negative adult male volunteers
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. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Surgery of gastrointestinal tract (except appendectomy)
3. 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. Chronic or relevant acute infections
6. History of allergy/hypersensitivity (including drug allergy) which was deemed relevant to the trial as judged by the investigator
7. Intake of drugs with a long half-life (>24 hours) within at least one month prior to study drug administration and during the trial
8. Use of drugs within 10 days prior to administration or during the trial which might reasonably influence the results of the trial
9. Participation in another trial with an investigational drug within two months prior to administration or during the trial
10. Current smoker
11. Alcohol abuse (more than 60 g/day)
12. Drug abuse (positive urine test for illicit prescription or non-prescription drugs or drugs of abuse)
13. Blood donation (more than 100 mL within four weeks prior to study drug administration or during the trial)
14. Excessive physical activities (within one week prior to study drug administration or during the trial)
15. Any laboratory value outside the reference range that was of clinical relevance at screening, according to the judgment of the investigator
16. Inability to comply with dietary regimen required by the protocol
17. Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, or hepatitis C antibody positive)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Group 1 - low dose; Treatment sequences ABC / CAB / BCA	Drug: Ritonavir; Drug: BILR 355 - Treatment A (current tablet formulation); Drug: BILR 355 - Treatment B (new tablet formulation); Drug: BILR 355 - Treatment C (new capsule formulation)
Experimental: Dose Group 2 - high dose; Treatment sequences DE / ED	Drug: Ritonavir; Drug: BILR 355 - Treatment D (current tablet formulation); Drug: BILR 355 - Treatment E (new capsule formulation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-inf (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	up to 96 hours after drug administration
Cmax (maximum measured concentration of analyte in plasma)	up to 96 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)	up to 96 hours after drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)	up to 96 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)	up to 96 hours after drug administration
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)	up to 96 hours after drug administration
Number of subjects with adverse events	up to 12 days following last drug administration
Number of subjects with abnormal changes in laboratory parameters	up to 48 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 30, 2014
• Last Verified: September 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: 1188.33