P-glypoprotein inhibition effect on the pharmacokinetics of two tacrolimus formulations: prolonged and extended-release

P-glypoprotein inhibition effect on the pharmacokinetics of two tacrolimus formulations: prolonged and extended-release - DIPLOID

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-001655-41-FR

Enrollment

Registered

2020-07-20

Start date

2020-09-15

Completion date

Unknown

Last updated

2023-10-03

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

Conditions

healthy volunteers

Interventions

Trade Name: Advagraf Product Name: Advagraf Pharmaceutical Form: Prolonged-release capsule, hard Trade Name: Envarsus Product Name: Envarsus Pharmaceutical Form: Prolonged-release tablet

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - adults (> 18 years) - Non smokers - Biological parameters within normal range (blood count, urea, creatinine, AST, ALT, GGT, bilirubine) - BMI within 18 and 25 - Negative urinary and plasma pregnancy test - Informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28

Exclusion criteria

Exclusion criteria: - participation to another study with incompatible procedure regarding the French law on research - Treatment with a drug drug interaction with tacrolimus - Cardiac rhythm at rest below 50 bpm - Cardiac issue detected on electrocardiogram - Cancer or history of cancer - Chronic infection or history of chronic infection - Diabetes or history of diabetes - Hypertension or history of hypertension - Pregnancy or lactation - Deprived of liberty (curatorship, guardianship or incarcerate)

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the P-gp inhibition on tacrolimus exposure in healthy volunteers administered Advagraf® or Envarsus®.;Secondary Objective: To evaluate the P-gp inhibition on intracellular tacrolimus pharmacokinetics in healthy volunteers administered Advagraf® or Envarsus®. To evaluate the intracellular diffusion between Advagraf® or Envarsus®. To evaluate the impact of ABCB1 genotypes on blood and intracellular exposure of tacrolimus. To evaluate the impact of other genotypes (coding for metabolism or drug transport) of interest on blood and intracellular exposure of tacrolimus. ;Primary end point(s): Change in area under the curve of tacrolimus blood concentrations between 0 and 24h.;Timepoint(s) of evaluation of this end point: Between 0 and 24 hour.	—

Measure

Time frame

Main Objective: To evaluate the P-gp inhibition on tacrolimus exposure in healthy volunteers administered Advagraf® or Envarsus®.;Secondary Objective: To evaluate the P-gp inhibition on intracellular tacrolimus pharmacokinetics in healthy volunteers administered Advagraf® or Envarsus®. To evaluate the intracellular diffusion between Advagraf® or Envarsus®. To evaluate the impact of ABCB1 genotypes on blood and intracellular exposure of tacrolimus. To evaluate the impact of other genotypes (coding for metabolism or drug transport) of interest on blood and intracellular exposure of tacrolimus. ;Primary end point(s): Change in area under the curve of tacrolimus blood concentrations between 0 and 24h.;Timepoint(s) of evaluation of this end point: Between 0 and 24 hour.

—

Secondary

Measure	Time frame
Secondary end point(s): - Blood pharmacokinetic parameters (peak concentration (Cmax), trough concentration (Cmin), Apparent clearance (Cl/F) and half-life (T1/2)). - Intracellular pharmacokinetic parameters (AUC, Cmax, Cmin, Cl/F, T1/2). - ABCB1 genotypes - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…). ;Timepoint(s) of evaluation of this end point: Blood pharmacokinetic parameters: Cmax Envarsus: 6-8 hour Cmax Advagraf: 2-3 hour Cmin: H24 Clearance: 0-24 hour Half-life: 0-24 hour Intracellular pharmacokinetic parameters: AUC: between 0 and 24 hour Cmax Envarsus: 6-8 hour Cmax Advagraf: 2-3 hour Cmin: H24 Clearance: 0-24 hour Half-life: 0-24 hour - ABCB1 génotypes: D0 - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…): D0	—

Measure

Time frame

Secondary end point(s): - Blood pharmacokinetic parameters (peak concentration (Cmax), trough concentration (Cmin), Apparent clearance (Cl/F) and half-life (T1/2)). - Intracellular pharmacokinetic parameters (AUC, Cmax, Cmin, Cl/F, T1/2). - ABCB1 genotypes - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…). ;Timepoint(s) of evaluation of this end point: Blood pharmacokinetic parameters: Cmax Envarsus: 6-8 hour Cmax Advagraf: 2-3 hour Cmin: H24 Clearance: 0-24 hour Half-life: 0-24 hour Intracellular pharmacokinetic parameters: AUC: between 0 and 24 hour Cmax Envarsus: 6-8 hour Cmax Advagraf: 2-3 hour Cmin: H24 Clearance: 0-24 hour Half-life: 0-24 hour - ABCB1 génotypes: D0 - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…): D0

—

Countries

France

Contacts

Public ContactLE NAOU

CHU de Rennes

dri@chu-rennes.fr33299282555

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026