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Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients (COLCHINCAL)

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01160276

First Posted: July 12, 2010

Last Update Posted: April 11, 2013

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

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

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

Purpose

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.

Condition	Intervention	Phase
Renal Replacement Therapies	Drug: cyclosporine+colchicine Drug: tacrolimus	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions Kidney Transplantation

Drug Information available for: Colchicine Cyclosporine Tacrolimus

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Half-life of colchicine (T1/2). [ 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 ]
Cmax observed colchicine. [ Time Frame: 4 weeks ]
Residual tacrolimus or cyclosporine concentrations [ Time Frame: 4 weeks ]
ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. [ Time Frame: 4 weeks ]
ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. [ 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 ]
GFR calculated by MDRD formula. [ Time Frame: 4 weeks ]
BMI [ Time Frame: 4 weeks ]
Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) [ Time Frame: 4 weeks ]


Enrollment:	17
Study Start Date:	May 2010
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Cyclosporine The first group is composed of 14 renal graft recipients under cyclosporine	Drug: 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. Other Names: Colchicine Colchimax
Active Comparator: Tacrolimus The second group is composed of 14 renal graft recipients under tacrolimus	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. Other Names: Colchicine Colchimax

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

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01160276

Locations


France
Assistance publique - Hôpitaux de Paris : Bicêtre Hospital
Le Kremlin Bicêtre, France, 94275

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

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

Investigators


Principal Investigator:	Antoine Jacquet, MD	Nephrology Department of BICETRE Hospital

More Information


Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01160276 History of Changes
Other Study ID Numbers:	P081105
First Submitted:	July 9, 2010
First Posted:	July 12, 2010
Last Update Posted:	April 11, 2013
Last Verified:	April 2013

Keywords provided by Assistance Publique - Hôpitaux de Paris:


renal graft colchicine drug interaction cyclosporine tacrolimus	renal transplantation renal transplant ABCB1 CYP3A5 SLCO1B1

Additional relevant MeSH terms:


Tacrolimus Cyclosporins Cyclosporine Calcineurin Inhibitors Colchicine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action	Antifungal Agents Anti-Infective Agents Dermatologic Agents Antirheumatic Agents Gout Suppressants Tubulin Modulators Antimitotic Agents Mitosis Modulators Antineoplastic Agents

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