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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01371006
First received: June 9, 2011
Last updated: July 3, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: low dose
Drug: normal dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Group A - Efavirenz: Cmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum plasma concentration (Cmax) of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  • Group A - Efavirenz: AUC0-∞ [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Faldaprevir: Cmax,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Faldaprevir: AUC0-12h,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Faldaprevir: C12,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Group A - Faldaprevir: Cmax,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum plasma concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  • Group A - Faldaprevir: Tmax,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group A - Faldaprevir: AUC0-12h,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group A - Faldaprevir: C12,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group A - Efavirenz: Tmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Time of maximum concentration of Efavirenz on day 14, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  • Group B - Faldaprevir: Tmax,ss [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Midazolam: Cmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Midazolam: Tmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Group B - Midazolam: AUC0-∞ [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG [ Time Frame: From first treatment administration (Day 1) up to Day 24 ] [ Designated as safety issue: No ]
    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.

  • Group A - Number of Participants With Drug Related Adverse Events [ Time Frame: 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) ] [ Designated as safety issue: No ]

    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.


  • Group B - Number of Participants With Drug Related Adverse Events [ Time Frame: From Day 1 up to 30 days after last treatment (Days 1,2,6,8,9,10,11,14,17,18,19,24) ] [ Designated as safety issue: No ]

    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.



Enrollment: 29
Study Start Date: June 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI201335 low dose Efavirenz
low dose Efavirenz
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: normal dose
efavirenz once daily

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371006

Locations
Switzerland
1220.20.41001 Boehringer Ingelheim Investigational Site
Basel, Switzerland
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01371006     History of Changes
Other Study ID Numbers: 1220.20
Study First Received: June 9, 2011
Results First Received: July 3, 2015
Last Updated: July 3, 2015
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Efavirenz
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2015