Effect of Multiple Dosing With BI 201335 on the Pharmacokinetics of Darunavir Co-administered With Ritonavir in Healthy Male and Female Volunteers

Effect of Multiple Dosing With 240 mg QD BI 201335 on the Steady-state Pharmacokinetics of 800 mg QD Darunavir Coadministered With 100 mg QD Ritonavir (DRV/r) in Healthy Male and Female Volunteers (an Open-label, Multiple-dose, Single Group, Single Fixed Sequence Phase I Study)

The objective of the current study is to investigate the effect of multiple oral daily doses of BI 201335 on the steady-state pharmacokinetics of darunavir co-administered with ritonavir.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: BI 201335; Drug: Darunavir; Drug: Ritonavir

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1220.49.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy male and female subjects according to the following criteria: medical history, physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram (ECG), clinical laboratory tests
2. Age 18 to 55 years (incl.)
3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.) and weight greater than 50 kg
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.

Exclusion criteria:

1. Any finding of the medical examination (including blood pressure (BP), pulse rate (PR) and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. History of photosensitivity or recurrent rash.
5. Surgery of the gastrointestinal tract (except appendectomy)
6. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
7. History of relevant orthostatic hypotension, fainting spells or blackouts.
8. Chronic or relevant acute infections
9. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
10. Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Smoker (more than 10 cigarettes)
13. Inability to refrain from smoking on trial days
14. Alcohol abuse (more than 30 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. ALT outside the normal range or any other laboratory value outside the reference range that is of clinical relevance
18. Inability to comply with dietary regimen of trial site
19. The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
20. Positive serology tests for Human immunodeficiency virus (HIV) and hepatitis B / C virus
21. Vulnerable subjects (e.g. persons kept in detention)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 201335; capsule for oral administration	Drug: BI 201335
Experimental: Darunavir 400 mg; tablet for oral administration	Drug: Darunavir; 400 mg tablet for oral administration
Experimental: Ritonavir 100 mg; tablet for oral administration	Drug: Ritonavir; tablet for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCτ,ss of Darunavir	area under the concentration-time curve of the analyte in plasma at steadystate over a uniform dosing interval τ of darunavir. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Cτ,ss of Darunavir	concentration of the analyte in plasma at steady-state after a uniform dosing interval τ=24h of darunavir	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)
Cmax,ss of Darunavir	maximum measured concentration of the analyte in plasma at steady-state	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 h after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax,ss of Darunavir	time from last dosing to maximum concentration of the analyte in plasma at steady state	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00,12:00 hours (h) after drug administration on day 8 (DRV/r) and day 16 (BI 201335+DRV/r)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 15, 2011
• First Posted (Estimate): June 16, 2011

Study Record Updates

• Last Update Posted (Estimate): July 31, 2015
• Last Update Submitted That Met QC Criteria: July 3, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; 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; Darunavir
• Other Study ID Numbers: 1220.49; 2011-000505-41 (EudraCT Number: EudraCT)