NCT01160276已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Area under the curve of plasma concentration of colchicine over time 0-∞
研究概览
简要总结
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.
详细描述
- 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cyclosporine
Active Comparator
The first group is composed of 14 renal graft recipients under cyclosporine
干预措施: cyclosporine+colchicine (Drug)
Tacrolimus
Active Comparator
The second group is composed of 14 renal graft recipients under tacrolimus
干预措施: tacrolimus (Drug)
结局指标
主要结局
Area under the curve of plasma concentration of colchicine over time 0-∞
时间窗: 4 weeks
次要结局
- Cmax observed colchicine.(4 weeks)
- ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.(4 weeks)
- 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)
- 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)
- BMI(4 weeks)
- Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII)(4 weeks)
- CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1.(4 weeks)
- GFR calculated by MDRD formula.(4 weeks)
研究者
研究点 (1)
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