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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

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ClinicalTrials.gov Identifier: NCT01371006
Recruitment Status : Completed
First Posted : June 10, 2011
Results First Posted : August 3, 2015
Last Update Posted : August 3, 2015
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

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 or disease Intervention/treatment Phase
Healthy Drug: low dose Drug: normal dose Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : June 2011
Actual Primary Completion Date : September 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Efavirenz
U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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 ]
    Maximum plasma concentration (Cmax) of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  2. 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 ]
    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)

  3. 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 ]
    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)

  4. 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 ]
    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)

  5. 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 ]
    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 :
  1. 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 ]
    Maximum plasma concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  2. 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 ]
    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)

  3. 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 ]
    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)

  4. 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 ]
    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)

  5. 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 ]
    Time of maximum concentration of Efavirenz on day 14, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)

  6. 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 ]
    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)

  7. 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 ]
    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)

  8. 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 ]
    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)

  9. 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 ]
    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)

  10. 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 ]
    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.

  11. 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) ]

    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.


  12. 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) ]

    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.




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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01371006


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

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01371006     History of Changes
Other Study ID Numbers: 1220.20
First Posted: June 10, 2011    Key Record Dates
Results First Posted: August 3, 2015
Last Update Posted: August 3, 2015
Last Verified: July 2015

Additional relevant MeSH terms:
Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers