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

This study has been completed.
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01160276
First received: July 9, 2010
Last updated: April 10, 2013
Last verified: April 2013
  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
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: 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:


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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Half-life of colchicine (T1/2). [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Cmax observed colchicine. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Residual tacrolimus or cyclosporine concentrations [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • GFR calculated by MDRD formula. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • BMI [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01160276     History of Changes
Other Study ID Numbers: P081105
Study First Received: July 9, 2010
Last Updated: April 10, 2013
Health Authority: France: Ministry of Health

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

ClinicalTrials.gov processed this record on July 29, 2014