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

Phase 1

• Conditions: healthy volunteers; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2020-001655-41-FR
• Lead Sponsor: CHU de Rennes

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-20
• Last Update Posted: 3 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 28

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

- 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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®.<br>To evaluate the intracellular diffusion between Advagraf® or Envarsus®.<br>To evaluate the impact of ABCB1 genotypes on blood and intracellular exposure of tacrolimus.<br>To evaluate the impact of other genotypes (coding for metabolism or drug transport) of interest on blood and intracellular exposure of tacrolimus.<br><br>;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 Outcome Measures

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