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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tacrolimus; Drug: Cyclosporine; Drug: Faldaprevir

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany
    • 1241.61.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Cyclosporine + Faldaprevir	Drug: Cyclosporine; Drug: Faldaprevir
Experimental: 2 Tacrolimus + Faldaprevir	Drug: Tacrolimus; Drug: Faldaprevir

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 20, 2013

Study Record Updates

• Last Update Posted (Estimate): May 23, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Tacrolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 1241.61; 2013-003435-30 (EudraCT Number: EudraCT)