Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients

NCT01160276 | Completed Phase 1 DMC

• 1 other identifier: P081105
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Replacement Therapies

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Area under the curve of plasma concentration of colchicine over time 0-∞

  4 weeks

Secondary Outcomes (10)

• Half-life of colchicine (T1/2).

  4 weeks

• AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp)

  4 weeks

• Cmax observed colchicine.

  4 weeks

• Residual tacrolimus or cyclosporine concentrations

  4 weeks

• ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group.

  4 weeks

Study Arms (2)

Cyclosporine

ACTIVE COMPARATOR

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

Drug: cyclosporine+colchicine

Tacrolimus

ACTIVE COMPARATOR

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

Drug: tacrolimus

Interventions

cyclosporine+colchicine 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.

Also known as: Colchicine, Colchimax

Cyclosporine

tacrolimus 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.

Also known as: Colchicine, Colchimax

Tacrolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Among the 14 patients with tacrolimus treatment:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Assistance publique - Hôpitaux de Paris : Bicêtre Hospital

Le Kremlin-Bicêtre, 94275, France

Location

MeSH Terms

Interventions

Colchicine; colchimax; Tacrolimus

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Antoine Jacquet, MD

  Nephrology Department of BICETRE Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 12, 2010
• Study Start: May 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: April 11, 2013

Record last verified: 2013-04

Locations

FR (1)