Comparison of Maximum Blood Concentrations of Colchicine Between Responders and Non-responders to Colchicine Treatment During Gout Flare
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Maximum plasma concentration of colchicine
研究概览
简要总结
Gout, secondary to sodium urate crystal deposition, is responsible of recurrent inflammatory painful flares. Efficacy of colchicine which is the first line drug for the treatment and prophylaxis of gout flare varies and only half of treated patients experience good response. This study aims to optimize colchicine prescription for the treatment and prophylaxis of gout flare.
Current data suggest that efficiency of colchicine relies on its maximum blood concentration (Cmax).
In this study, the investigators hypothesize that responders to colchicine treatment have higher colchicine Cmax than non-responder patients following the recommended dose regimen (1 mg then 0.5 mg 1 hour later).
The individual pharmacokinetics (PK) of colchicine remains poorly investigated while the assessment of individual drug metabolisms can be performed.
The hypothesis of this study stands that several factors contribute to the variability of colchicine Cmax. The analysis of individual PK profile and a well-characterized metabolism of colchicine will permit a personalized treatment regimen for the treatment and prophylaxis of gout flares.
详细描述
Gout flare is driven by interleukin (IL)-1β production and can be treated by colchicine, NSAID, corticoid or IL-1β blockers (PMID 27457514).
Colchicine is an alkaloid compound that disrupts cytoskeletal functions through inhibition of microtubule polymerization and consequently interferes with the intracellular assembly of the inflammasome NLRP3 complex that mediates activation of IL-1β (PMID 16407889).
Efficacy of colchicine treatment in gout flare varies between 37.5 and 64% (PMID 3314832; 20131255). Previous study suggests that colchicine efficiency relies on its blood maximum concentration (Cmax) (PMID 20131255). However this hypothesis needs to be confirmed.
The hypothesis of this study stands that colchicine Cmax varies with individual colchicine pharmacokinetics and that this individual variation may explain the variation response of colchicine treatment.
Absorption of orally administrated colchicine varies between 24 et 88% with an average of 45%. Thus, following oral administration of 1.8 mg colchicine over 1 hour to healthy young adults, under fasting condition, the colchicine Cmax (mean 6.2 ng/ml) is reached within a median of 1.8 hours (range 1.0-2.5) (PMID 20131255).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
all participants will perform the pharmacokinetic study and take colchicine 1 mg + 0.5 mg 1 hour later, midazolam 1 mg and fexofenadine 120 mg.
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 (> 18 years old) with gout flare defined by following items :
- •Identification of sodium urate crystals in synovial fluid analysis
- •Or gout flare diagnosis according to Nijmegen criteria (score > 8/13)
- •Man (2 pts)
- •History of flare (2 pts)
- •Flare involving first metatarsophalangeal joint (2.5 pts)
- •Maximum of flare within 24h (0.5pt),
- •Redness (1 pt),
- •History of hypertension or cardiovascular diseases (1.5 pts),
- •Serum urate level > 360 µmol/l during flare (3.5 pts)
- •Duration of flare < 48 h
- •Monoarticular involvement
排除标准
- •Hypersensitivity to colchicine, fexofenadine, benzodiazepine or the excipients of these drugs
- •Contra-indication to colchicine : chronic kidney disease stage 4-5, severe hepatic impairment, treatment by macrolide antibiotics
- •Used of pain-killers other than acetaminophen
- •Involvement in another clinical trial with drug administration
- •Illiteracy
- •Pregnant woman or breastfeeding
研究组 & 干预措施
Pharmacokinetic study
all participants will undergo pharmacokinetic study and take colchicine (1.5 mg over 1 hour), midazolam (1 mg) and fexofenadine (120 mg)
干预措施: Colchicine, (Drug)
Pharmacokinetic study
all participants will undergo pharmacokinetic study and take colchicine (1.5 mg over 1 hour), midazolam (1 mg) and fexofenadine (120 mg)
干预措施: midazolam, (Drug)
Pharmacokinetic study
all participants will undergo pharmacokinetic study and take colchicine (1.5 mg over 1 hour), midazolam (1 mg) and fexofenadine (120 mg)
干预措施: fexofenadine (Drug)
结局指标
主要结局
Maximum plasma concentration of colchicine
时间窗: From drug administration to 6 hour post-drug administration
Maximum plasma concentration of colchicine in responders and non-responders to colchicine treatment for gout flare during pharmacokinetic study performed 1 month after flare resolution and before initiation of urate-lowering therapy.
次要结局
- Area under the curve [AUC](From drug administration to 6 hour post-drug administration)
- Maximum Plasma Concentration [Cmax](From drug administration to 6 hour post-drug administration)
- Time needed to reach Cmax [Tmax ](From drug administration to 6 hour post-drug administration)
- Volume of distribution [Vd](From drug administration to 6 hour post-drug administration)
- Absorption rate constant [Ka](From drug administration to 6 hour post-drug administration)
- Clearance(From drug administration to 6 hour post-drug administration)