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)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02016625

Enrollment

Registered

2013-12-20

Start date

2013-12-31

Completion date

2014-04-30

Last updated

2016-05-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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

Interventions

DRUGFaldaprevir

DRUGCyclosporine

DRUGTacrolimus

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
AUC 0-infinity (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	up to 168 hours (details in description)	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)	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). 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)	up to 168 hours (details in description)	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)	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). 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)	up to 168 hours (details in description)	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)	up to 168 hours (details in description)	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)	up to 192 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). 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)	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). 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)	up to 192 hours (details in description)	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)	up to 168 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). 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)	up to 168 hours (details in description)	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)	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). 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.

Countries

Germany

Participant flow

Recruitment details

The trial was nonrandomised, open-label and fixed-sequence and was performed in 2 separate groups of 2 periods each in healthy male and female volunteers. Treatments for the two periods were in group 1 cyclosporine (cyclo) and cyclo and faldaprevir (FDV), and in Group 2 tacrolimus (tac) and tac and FDV.

Participants by arm

Arm	Count
Cyclosporine / Cyclosporine + Faldaprevir fixed sequence group 1: single dose of 50 mg cyclo on Day 1 in period 1; treated with FDV 240 mg on Day -7 (loading dose) and 120 mg FDV on Days -6 to 7 and a single dose of 50 mg cyclo on Day 1 in period 2. Mode of administration: oral, with 240 mL water after a meal. A washout period of at least 14 days separated administration of cyclo in the treatment periods.	16
Tacrolimus / Tacrolimus + Faldaprevir fixed sequence group 2: single dose of 0.5 mg tac on Day 1 in period 1; treated with FDV 240 mg on Day -7 (loading dose) and 120 mg FDV on Days -6 to 7 and a single dose of 0.5 mg tac on Day 1 in period 2. Mode of administration: oral, with 240 mL water after a meal. A washout period of at least 14 days separated administration of cyclo in the treatment periods.	15
Total	31

Withdrawals & dropouts

Period	Reason	FG000	FG001
Cyclo or Tac (Day 1) + FDV (Day -7 to 7)	Adverse Event	1	0
Cyclo or Tac (Day 1) + FDV (Day -7 to 7)	not specified above	2	0
Cyclo or Tac (Single Dose, Day 1)	not treated	0	1

Baseline characteristics

Characteristic	Cyclosporine / Cyclosporine + Faldaprevir	Tacrolimus / Tacrolimus + Faldaprevir	Total
Age, Continuous	41.2 years STANDARD_DEVIATION 8.3	41.5 years STANDARD_DEVIATION 8.8	41.3 years STANDARD_DEVIATION 8.4
Sex: Female, Male Female	8 Participants	6 Participants	14 Participants
Sex: Female, Male Male	8 Participants	9 Participants	17 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 16	5 / 15	10 / 15	7 / 15	4 / 14	5 / 15
serious Total, serious adverse events	0 / 16	0 / 15	0 / 15	0 / 15	0 / 14	1 / 15

Outcome results

Primary

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.

Time frame: up to 168 hours (details in description)

Population: pharmacokinetic set of cyclo (PKS cyclo): The subject set for the evaluation of PK endpoints was to include all treated subjects who provided at least 1 observation of cyclo in plasma for at least 1 primary endpoint, and who did not have important protocol violations with respect to the statistical evaluation of PK endpoints.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	AUC 0-infinity (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	672 ng*h/mL	Geometric Coefficient of Variation 17.4
Cyclosporine + Faldaprevir	AUC 0-infinity (Area Under the Concentration-time Curve of the Cyclo in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	732 ng*h/mL	Geometric Coefficient of Variation 25.1

Comparison: Geometric mean (gMean) ratio of cyclo + FDV to cyclo treatment. The statistical model used for the analysis of primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. This model accounted for variation from 'subject' and 'treatment' effects. The 'subject' effect was considered to be random, whereas the 'treatment' effect was considered as fixed.p-value: 0.003390% CI: [99.992, 117.076]ANOVA

Primary

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

Time frame: up to 192 hours (details in description)

Population: pharmacokinetic set of tac (PKS tac): The subject set for the evaluation of PK endpoints was to include all treated subjects who provided at least 1 observation of tac in plasma for at least 1 primary endpoint, and who did not have important protocol violations with respect to the statistical evaluation of PK endpoints.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	AUC 0-infinity (Area Under the Concentration-time Curve of the Tac in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	16.0 ng*h/mL	Geometric Coefficient of Variation 57.6
Cyclosporine + Faldaprevir	AUC 0-infinity (Area Under the Concentration-time Curve of the Tac in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	20.4 ng*h/mL	Geometric Coefficient of Variation 62.9

Comparison: gMean ratio of tac+FDV to FDV treatment. The statistical model used for the analysis of primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. This model accounted for variation from 'subject' and 'treatment' effects. The 'subject' effect was considered to be random, whereas the 'treatment' effect was considered as fixed.p-value: 0.620790% CI: [114.453, 141.827]ANOVA

Primary

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.

Time frame: up to 168 hours (details in description)

Population: PKS cyclo

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	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)	635 ng*h/mL	Geometric Coefficient of Variation 16.2
Cyclosporine + Faldaprevir	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)	685 ng*h/mL	Geometric Coefficient of Variation 25.2

Comparison: gMean ratio of cyclo+FDV to cyclo treatment The statistical model used for the analysis of primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. This model accounted for variation from 'subject' and 'treatment' effects. The 'subject' effect was considered to be random, whereas the 'treatment' effect was considered as fixed.p-value: 0.001990% CI: [98.36, 115.534]ANOVA

Primary

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

Time frame: up to 192 hours (details in description)

Population: PKS tac

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	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)	11.1 ng*h/mL	Geometric Coefficient of Variation 62.8
Cyclosporine + Faldaprevir	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)	15.3 ng*h/mL	Geometric Coefficient of Variation 66.2

Primary

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

Time frame: up to 168 hours (details in description)

Population: PKS cyclo + treated with FDV alone (arm: Faldaprevir) or started combination treatment FDV+cyclosporine in treatment period 2.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	AUC τ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)	24600 ng*h/mL	Geometric Coefficient of Variation 196
Cyclosporine + Faldaprevir	AUC τ,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)	30600 ng*h/mL	Geometric Coefficient of Variation 267

Comparison: gMean ratio of cyclo+FDV to FDV treatment. The statistical model used for the analysis of primary endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. This model accounted for variation from 'subject' and 'treatment' effects. The 'subject' effect was considered to be random, whereas the 'treatment' effect was considered as fixed.p-value: 0.418190% CI: [104.8, 143.6]ANOVA

Primary

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.

Time frame: up to 168 hours (details in description)

Population: PKS tac

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	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)	40300 ng*h/mL	Geometric Coefficient of Variation 39.1
Cyclosporine + Faldaprevir	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)	38700 ng*h/mL	Geometric Coefficient of Variation 48.3

Primary

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.

Time frame: up to 168 hours (details in description)

Population: PKS tac

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	C24,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a 24 Hour Dosing Interval)	904 ng/mL	Geometric Coefficient of Variation 56.1
Cyclosporine + Faldaprevir	C24,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a 24 Hour Dosing Interval)	900 ng/mL	Geometric Coefficient of Variation 52.1

Primary

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

Time frame: up to 168 hours (details in description)

Population: PKS cyclo + treated with FDV alone (arm: Faldaprevir) or started combination treatment FDV+cyclosporine in treatment period 2.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	C24,ss (Maximum Measured Concentration of the FDV in Plasma at Steady State Over a 24 Hour Dosing Interval)	619 ng/mL	Geometric Coefficient of Variation 194
Cyclosporine + Faldaprevir	C24,ss (Maximum Measured Concentration of the FDV in Plasma at Steady State Over a 24 Hour Dosing Interval)	723 ng/mL	Geometric Coefficient of Variation 205

Primary

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

Time frame: up to 168 hours (details in description)

Population: PKS cyclo

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	Cmax (Maximum Measured Concentration of the Cyclo in Plasma)	172 ng/mL	Geometric Coefficient of Variation 34.7
Cyclosporine + Faldaprevir	Cmax (Maximum Measured Concentration of the Cyclo in Plasma)	164 ng/mL	Geometric Coefficient of Variation 27.8

Primary

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

Time frame: up to 192 hours (details in description)

Population: PKS tac

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	Cmax (Maximum Measured Concentration of the Tac in Plasma)	1.14 ng/mL	Geometric Coefficient of Variation 35.5
Cyclosporine + Faldaprevir	Cmax (Maximum Measured Concentration of the Tac in Plasma)	1.13 ng/mL	Geometric Coefficient of Variation 48.9

Primary

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

Time frame: up to 168 hours (details in description)

Population: PKS cyclo + treated with FDV alone (arm: Faldaprevir) or started combination treatment FDV+cyclosporine in treatment period 2.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Cyclo Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)	1740 ng/mL	Geometric Coefficient of Variation 225
Cyclosporine + Faldaprevir	Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Cyclo Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)	2470 ng/mL	Geometric Coefficient of Variation 331

Primary

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.

Time frame: up to 168 hours (details in description)

Population: PKS tac

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cyclosporine	Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)	3120 ng/mL	Geometric Coefficient of Variation 35.7
Cyclosporine + Faldaprevir	Cmax,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)	2930 ng/mL	Geometric Coefficient of Variation 51.3

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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 Tac in Plasma Over the Time Interval From 0 Extrapolated to Infinity)

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 Tac in Plasma Over the Time Interval From 0 to the Last Quantifiable Point)

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 [Followed by Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)

C24,ss (Maximum Measured Concentration of the FDV [Followed by Tac Treatment] in Plasma at Steady State Over a 24 Hour Dosing Interval)

C24,ss (Maximum Measured Concentration of the FDV in Plasma at Steady State Over a 24 Hour Dosing Interval)

Cmax (Maximum Measured Concentration of the Cyclo in Plasma)

Cmax (Maximum Measured Concentration of the Tac in Plasma)

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 Tac Treatment] in Plasma at Steady State Over a Uniform Dosing Interval τ)