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

Study Overview
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Brief Summary
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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

Official Title
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Investigation of Potential Drug-drug Interactions Between Faldaprevir and Immunosuppressants (Cyclosporine and Tacrolimus) in Healthy Male and Female Subjects (Open-label, Fixed-sequence Trial)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Faldaprevir
* Drug: Faldaprevir
* Drug: Cyclosporine
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Cyclosporine + Faldaprevir<br> | Drug: Faldaprevir<br> <br> Drug: Cyclosporine<br> <br> |
| Experimental: 2 Tacrolimus + Faldaprevir<br> | Drug: Faldaprevir<br> <br> Drug: Tacrolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-infinity (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 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. | up to 168 hours (details in description) | 
| 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) | 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. | up to 168 hours (details in description) | 
| Cmax (Maximum Measured Concentration of the Cyclo in Plasma) | 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 | up to 168 hours (details in description) | 
| Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Cyclo Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ) | 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 | up to 168 hours (details in description) | 
| C24,ss (Maximum Measured Concentration of the FDV in Plasma at Steady State Over a 24 Hour Dosing Interval) | 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 | up to 168 hours (details in description) | 
| AUC τ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ) | 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 | up to 168 hours (details in description) | 
| AUC 0-infinity (Area Under the Concentration-time Curve of the Tac in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 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 | up to 192 hours (details in description) | 
| 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) | 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 | up to 192 hours (details in description) | 
| Cmax (Maximum Measured Concentration of the Tac in Plasma) | 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 | up to 192 hours (details in description) | 
| Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ) | 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. | up to 168 hours (details in description) | 
| C24,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a 24 Hour Dosing Interval) | 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. | up to 168 hours (details in description) | 
| 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) | 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. | up to 168 hours (details in description) |