Evaluation of the Effect of Multiple Dosing With BI 201335 on CYP2B6 Metabolism and Effect of Multiple Dosing With Efavirenz on the Steady-state Pharmacokinetics of BI 201335 and on CYP3A4/5 Metabolism in Healthy Volunteers

Effect of Multiple Dosing With 240mg q 12hrs BI 201335 on the Pharmacokinetics of 50 mg Single Dose Efavirenz and Effect of Multiple Dosing With 600mg QD Efavirenz on Cyp 3A4 and the Pharmacokinetics of BI 201335 in Healthy Volunteers

Obtain interaction data between BI 201335 and Efavirenz to guide dosing for each drug when administered together.

To predict drug interaction between BI 201335 and Cyp 3A4 y using Midazolam as cyp 3A4 probe , Efavirenz as enzyme inducer and BI 201335 as enzyme inhibitor.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: low dose; Drug: low dose; Drug: normal dose

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • 1220.20.41001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Healthy volunteers age 18- 55 BMI (Body Mass Index) 18.5 - 29.9

Exclusion criteria:

1. Any finding on medical examination and ECG (Electrocardiography) deviating from normal
2. Active diseases
3. History of photosensitivity or rash

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI201335 low dose Efavirenz; low dose Efavirenz	Drug: low dose; efavirenz single dosing once daily; Drug: low dose; Efavirenz single dosing once daily
Experimental: BI201335 high dose Efavirenz; normal dose Efavirenz	Drug: low dose; efavirenz single dosing once daily; Drug: low dose; Efavirenz single dosing once daily; Drug: normal dose; efavirenz once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group A - Efavirenz: Cmax	Maximum plasma concentration (Cmax) of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 hours(h) after administration of Efavirenz
Group A - Efavirenz: AUC0-∞	Area under the concentration-time curve of the analyte in plasma over the time interval 0 to infinity of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 h after administration of Efavirenz
Group B - Faldaprevir: Cmax,ss	Maximum plasma concentration at steady state of Faldaprevir calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir
Group B - Faldaprevir: AUC0-12h,ss	Area under the concentration-time curve of Faldaprevir at steady state over the time interval 0 to 12h calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir
Group B - Faldaprevir: C12,ss	Plasma concentration 12 h after dosing of Faldaprevir at steady state calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group A - Faldaprevir: Cmax,ss	Maximum plasma concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Group A - Faldaprevir: Tmax,ss	Time of maximum concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Group A - Faldaprevir: AUC0-12h,ss	Area under the concentration-time curve of Faldaprevir over the time interval 0-12h on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Group A - Faldaprevir: C12,ss	Plasma concentration 12 h after dosing of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Group A - Efavirenz: Tmax	Time of maximum concentration of Efavirenz on day 14, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Efavirenz
Group B - Faldaprevir: Tmax,ss	Time of maximum concentration of Faldaprevir on Day 9 and 10 at steady state, calculated for patients in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Group B - Midazolam: Cmax	Maximum plasma concentration of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Group B - Midazolam: Tmax	Time of maximum concentration after a single dose of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Group B - Midazolam: AUC0-∞	Area under the concentration-time curve of of Midazolam over the time interval 0 to infinity on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)	0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG	Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.	From first treatment administration (Day 1) up to Day 24
Group A - Number of Participants With Drug Related Adverse Events	Number of participants with investigator-defined drug related adverse events (AE) in sequence group A. AEs occurring up to 5 days after last intake of Faldaprevir on day 19 were assigned to Efavirenz+Faldaprevir treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone.	From Day 1 up to 30 days after last treatment (Days 1,2,3,4,5,6,7,8,11,13,14,15,16,17,18,19,20,24)
Group B - Number of Participants With Drug Related Adverse Events	Number of participants with investigator-defined drug related adverse events (AE) in sequence group B. AEs occurring up to 5 days after last intake of Faldaprevir were assigned to Faldaprevir+Midazolam+Efavirenz treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone.	From Day 1 up to 30 days after last treatment (Days 1,2,6,8,9,10,11,14,17,18,19,24)

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): September 1, 2011

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimate): June 10, 2011

Study Record Updates

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

More Information

Terms related to this study

• Other Study ID Numbers: 1220.20