Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients

NCT ID: NCT01160276

Last Updated: 2013-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2012-01-31

Brief Summary

Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition.

This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.

Detailed Description

• Renal transplantation >= one year
• eGFR (MDRD) > 30ml/min
• hemoglobin >= 11g/dl
• treatment with tacrolimus or cyclosporine
• no previous muscular disease
• no drugs interfering with P-glycoprotein or CYP3A activity or expression outcomes
• colchicine AUC, Cmax, T1/2
• ABCB1C3435T, CYP3A5 and SLCO1B1 genotypes

Conditions

Renal Replacement Therapies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclosporine

The first group is composed of 14 renal graft recipients under cyclosporine

Group Type: ACTIVE_COMPARATOR

cyclosporine+colchicine

Intervention Type: DRUG

the 14 patients of the 1st group are under cyclosporine and One pill of colchimax 1mg will be taken by all the patients at Day 3.

Tacrolimus

The second group is composed of 14 renal graft recipients under tacrolimus

Group Type: ACTIVE_COMPARATOR

tacrolimus

Intervention Type: DRUG

the 14 patients of the second group are under tacrolimus and One pill of colchimax 1mg will be taken by all the patients at Day 3.

Interventions

cyclosporine+colchicine

the 14 patients of the 1st group are under cyclosporine and One pill of colchimax 1mg will be taken by all the patients at Day 3.

Intervention Type: DRUG

tacrolimus

the 14 patients of the second group are under tacrolimus and One pill of colchimax 1mg will be taken by all the patients at Day 3.

Intervention Type: DRUG

Other Intervention Names

Colchicine; Colchimax; Colchicine; Colchimax

Eligibility Criteria

Inclusion Criteria

• Patients with renal graft since at least 1 year
• Patients treated with ciclosporin or tacrolimus
• Are at least 18 years old.
• Glomerular filtration rate above 30 ml / min calculated using the MDRD formula
• Among the 14 patients receiving ciclosporin:
• The genotype is not a criterion for inclusion
• Among the 14 patients with tacrolimus treatment:
• 7 genotype ABCB1 3435CC, 7 genotype ABCB1 3435TT
• Recent (1 month) residual concentration of tacrolimus between 5-10ng/ml
• Recent (1 month) residual concentration of ciclosporin between 100-200ng/ml
• For women : a negative pregnancy test (serum beta hCG)
• Realization of a medical examination.
• Informed consent and writing form.

Exclusion Criteria

• Abnormal transaminases (AST and ALT above the ULN Laboratory).
• Underlying Liver Disease (steatosis, cirrhosis, chronic hepatitis, the virus of hepatitis C or B).
• Previous history of muscle disease (drug related especially the statin type).
• Leukopenia (WBC <3000/mm3).
• Hemoglobin <11g/dl.
• Patient treated by erythropoetin (whatever its hemoglobin value).
• Abnormal CPK (greater than the ULN Laboratory).
• Prior intolerance to colchicine.
• Regular intake of the following medications associated with rhabdomyolyses: antipsychotics, cholesterol lowering agents (statins or fibrates), zidovudine, antidepressants (selective inhibitor of serotonin reuptake) and lithium.
• Patient (e) can not refrain from consuming grapefruit juice.
• Patient (e) taking a tea based on St John's wort.
• Taking drugs inducers of P-gp or CYP3A4 (rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, protease inhibitors, griseofulvin).
• Taking drugs inhibitors of P-gp or CYP3A4 (quinidine, macrolide antibiotics, azole antifungals, protease inhibitors, amiodarone, diltiazem, verapamil).
• Chronic diarrhea.
• ABCB1 Genotype 3435CT for patients in the tacrolimus group.
• Participation in another concurrent trial.
• Patient (e) exclusion period of another trial.
• Patient (e) having reached the maximum annual amount of compensation provided by law.
• No affiliation to French social security scheme or without CMU.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoine Jacquet, MD

Role: PRINCIPAL_INVESTIGATOR

Nephrology Department of BICETRE Hospital

Locations

Assistance publique - Hôpitaux de Paris : Bicêtre Hospital

Le Kremlin-Bicêtre, , France

Countries

France

Other Identifiers

P081105

Identifier Type: -

Identifier Source: org_study_id