Investigation of Potential Drug-drug Interactions Between Faldaprevir and the Immunosuppressant Drugs Cyclosporine or Tacrolimus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02016625
First received: December 16, 2013
Last updated: April 21, 2016
Last verified: April 2016
  Purpose
The primary objective of this trial is to investigate the effect of multiple-dose faldaprevir (FDV) on the single-dose pharmacokinetics of cyclosporine or tacrolimus

Condition Intervention Phase
Healthy
Drug: Faldaprevir
Drug: Cyclosporine
Drug: Tacrolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigation of Potential Drug-drug Interactions Between Faldaprevir and Immunosuppressants (Cyclosporine and Tacrolimus) in Healthy Male and Female Subjects (Open-label, Fixed-sequence Trial)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • AUC 0-infinity (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 Extrapolated to Infinity) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    AUC 0-infinity (area under the concentration-time curve of the cyclo in plasma over the time interval from 0 extrapolated to infinity).

    PK sampling (relative to the first cyclo administration [h:min])

    Period 1:

    for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h.

    period 2 for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h.


  • AUC 0-tz (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 to the Last Quantifiable Point) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    AUC 0-tz (area under the concentration-time curve of the cyclo in plasma over the time interval from 0 to the last quantifiable point).

    PK sampling (relative to the first cyclo administration [h:min]):

    Period 1:

    for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h period 2 for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h.


  • Cmax (Maximum Measured Concentration of the Cyclo in Plasma) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    Cmax (maximum measured concentration of the cyclo in plasma).

    PK sampling (relative to the first cyclo administration [h:min]):

    Period 1: for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h period 2 for cyclo 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Cyclo Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    Cmax,ss (maximum measured concentration of the FDV [followed by cyclo treatment] in plasma at steady state over a uniform dosing interval τ).

    PK sampling (relative to the first cyclo administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • C24,ss (Maximum Measured Concentration of the FDV in Plasma at Steady State Over a 24 Hour Dosing Interval) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    PK sampling (relative to the first cyclo administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • AUC τ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    AUC τ,ss (area under the concentration-time curve of the FDV in plasma at steady state over a uniform dosing interval τ).

    PK sampling (relative to the first cyclo administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • AUC 0-infinity (Area Under the Concentration-time Curve of the Tac in Plasma Over the Time Interval From 0 Extrapolated to Infinity) [ Time Frame: up to 192 hours (details in description) ] [ Designated as safety issue: No ]

    AUC 0-infinity (area under the concentration-time curve of the tac in plasma over the time interval from 0 extrapolated to infinity).

    PK sampling (relative to the first tac administration):

    Period 1: for tac 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 144:00h, 168:00h, 192:00h period 2 for tac

    -192:00h, -168:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • AUC 0-tz (Area Under the Concentration-time Curve of the Tac in Plasma Over the Time Interval From 0 to the Last Quantifiable Point) [ Time Frame: up to 192 hours (details in description) ] [ Designated as safety issue: No ]

    AUC 0-tz (area under the concentration-time curve of the tac in plasma over the time interval from 0 to the last quantifiable point).

    PK sampling (relative to the first tac administration [h:min]):

    Period 1: for tac

    0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 144:00h, 168:00h, 192:00h

    Period 2 For tac

    -192:00h, -168:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • Cmax (Maximum Measured Concentration of the Tac in Plasma) [ Time Frame: up to 192 hours (details in description) ] [ Designated as safety issue: No ]

    Cmax (maximum measured concentration of the tac in plasma).

    PK sampling (relative to the first tac administration [h:min]):

    Period 1:

    for tac 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 144:00h, 168:00h, 192:00h Period 2 For tac

    -192:00h, -168:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h


  • Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    Cmax,ss (maximum measured concentration of the FDV [followed by tac treatment] in plasma at steady state over a uniform dosing interval τ).

    PK sampling (relative to the first tac administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h.


  • C24,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a 24 Hour Dosing Interval) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    PK sampling (relative to the first tac administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h.


  • AUC τ,ss (Area Under the Concentration-time Curve of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ) [ Time Frame: up to 168 hours (details in description) ] [ Designated as safety issue: No ]

    AUC τ,ss (area under the concentration-time curve of the FDV [followed by tac treatment] in plasma at steady state over a uniform dosing interval τ).

    PK sampling (relative to the first cyclo administration [h:min]):

    period 2 For FDV

    -144:00h, -120:00h, -96:00h, -72:00h, -48:00h, -24:00h, -23:30h, -23:00h, -22:30h, -22:00h, -21:00h, -20:00h, -18:00h, -16:00h, -14:00h, -12:00h, -8:00h, 0:00h, 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 16:00h, 24:00h, 48:00h, 72:00h, 96:00h, 120:00h, 144:00h, 168:00h.



Enrollment: 32
Study Start Date: December 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Cyclosporine + Faldaprevir Drug: Faldaprevir Drug: Cyclosporine
Experimental: 2 Tacrolimus + Faldaprevir Drug: Faldaprevir Drug: Tacrolimus

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Healthy males or females subjects
  • Age 18 to 50 years (incl.)
  • Body mass index (BMI) 18.5 to 29.9 kg/m2 (incl.)
  • Signed and dated written informed consent prior to admission to the study

Exclusion criteria:

  • Any finding in the medical examination (including blood pressure, pulse rate or ECG) deviating from normal and judged clinically relevant by the investigator.
  • Systolic blood pressure (BP) less than 100 mmHg and more than 140 mmHg.
  • Diastolic BP less than 60 mmHg and more than 90 mmHg.
  • Pulse rate (PR) less than 50 bpm and more than 90 bpm.
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged clinically relevant by the investigator
  • Positive QuantiFERON-TB Gold In-Tube
  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: NCT02016625

Locations
Germany
1241.61.1 Boehringer Ingelheim Investigational Site
Mannheim, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02016625     History of Changes
Other Study ID Numbers: 1241.61  2013-003435-30 
Study First Received: December 16, 2013
Results First Received: January 21, 2016
Last Updated: April 21, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Tacrolimus
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 21, 2016