Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01160276
• Date of registration: 09/07/2010
• Prospective Registration: No
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients COLCHINCAL
• Scientific title: An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients
• Date of first enrolment: May 2010
• Target sample size: 17
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01160276
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: Antoine Jacquet, MD
• Affiliation: Nephrology Department of BICETRE Hospital

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Renal Replacement Therapies

Intervention(s)

Drug: cyclosporine+colchicine

Drug: tacrolimus

Primary Outcome(s)

Area under the curve of plasma concentration of colchicine over time 0-8 [Time Frame: 4 weeks]

Secondary Outcome(s)

ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. [Time Frame: 4 weeks]

BMI [Time Frame: 4 weeks]

Residual tacrolimus or cyclosporine concentrations [Time Frame: 4 weeks]

GFR calculated by MDRD formula. [Time Frame: 4 weeks]

Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) [Time Frame: 4 weeks]

ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. [Time Frame: 4 weeks]

AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp) [Time Frame: 4 weeks]

CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1. [Time Frame: 4 weeks]

Cmax observed colchicine. [Time Frame: 4 weeks]

Half-life of colchicine (T1/2). [Time Frame: 4 weeks]

Secondary ID(s)

P081105

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

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