Evaluation of the Impact of Renal Function on the Pharmacokinetics of Hydroxyurea (SIKLOS ®) in Normal-renal Function, Hyperfiltrating and Renal Failure Sickle Cell Disease Patients (DARH)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Theravia
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Measure of Plasmatic Data: Maximum Concentration (Cmax)
研究概览
简要总结
The use of hydroxyurea in sickle cell disease patients with glomerular hyperfiltration and renal failure requires a specific monitoring and dose adjustment in order to remain within the therapeutic interval while limiting the risk of toxicity or therapeutic failure. For this reason the investigators propose to compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Age ≥ 18 years.
- •Male or female.
- •Sickle cell disease (SS or S-β0thal) confirmed by haemoglobin electrophoresis and genotyping by deoxyribonucleic acid (DNA) analysis.
- •Affiliation to a social security system.
- •Having freely consented in writing after being informed of the objective, programme and potential risks incurred.
- •These criteria will apply to the 3 groups of sickle cell disease patients according to the renal function stage defined by the glomerular filtration rate (GFR) estimated by the formula of the Chronic Kidney Disease EPIdemiology (CKD EPI) collaboration without ethnic criterion during the last 6 months before inclusion:
- •Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men.
- •Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m
- •Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
- •Treated with hydroxyurea (Siklos®) with a stable dosage for at least one week ± 2 days before inclusion in the study and dose administered in the morning at 9:00 ± 15 minutes.
排除标准
- •Refusal to consent.
- •Patients that do not comply.
- •Occurrence of vaso-occlusive crisis in the month prior to the inclusion in the study.
- •Patients having had an exchange transfusion in the 15 days before inclusion in the study.
- •Patients participating in another clinical trial or in the exclusion period of a previous clinical trial.
- •Patients treated with a diuretic.
- •Dialysis patient.
- •Patients with an intercurrent disorder, especially inflammatory, that has not recovered for at least one month.
- •Pregnant or breast-feeding women.
- •Patients deprived of liberty or under legal protection.
- •Patients who cannot understand the objective and the course of the study, incapable of giving their consent.
- •In the event of severe hepatic failure.
- •In the event of severe renal failure (creatinine clearance < 30 ml/min).
- •Patients who show toxic signs of bone marrow suppression.
研究组 & 干预措施
Normal-renal function
Normal-renal function: 90 ≤ GFR ≤ 130 mL/min/1.73m2 in women or 140 mL/min/1.73m2 in men
干预措施: Siklos (Drug)
Glomerular hyperfiltration
Glomerular renal hyperfiltration: GFR > 130 mL/min/1.73m2 in women and GFR > 140 mL/min/1.73m2 in men.
干预措施: Siklos (Drug)
Moderate renal failure
Moderate renal failure: 30 ≤ GFR ≤ 60 mL/min/1.73m2
干预措施: Siklos (Drug)
结局指标
主要结局
Measure of Plasmatic Data: Maximum Concentration (Cmax)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Minimum Concentration (Cmin)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Elimination Half-life (T½)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Total Clearance (Cl Tot)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Time to Obtain the Maximum Concentration (Tmax)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Area Under the Curve (AUC0-24)
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Plasmatic Data: Distribution Volume
时间窗: 0 hour, 0.75 hour, 1.5 hours, 3 hours, 4 hours, 6 hours, 7.5 hours , 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Urinary Data: Hydroxyurea Urinary Fractions
时间窗: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
Measure of Urinary Data: Renal Clearance (Cl Renal).
时间窗: From 0 to 4 hours, 4 to 7.5 hours and 7.5 to 24 hours
Compare the pharmacokinetic parameters of hydroxyurea in normal-renal function sickle cell patients to those of patients with glomerular hyperfiltration or moderate renal failure
次要结局
未报告次要终点