A Single-center, Open-label, Randomized, Versus a Control Group, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Oral Lucerastat in Adult Subjects With Fabry Disease Receiving Enzyme Replacement Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of subjects with treatment-emergent adverse events and serious adverse events
研究概览
简要总结
The primary purpose of this study was to assess the safety and tolerability of lucerastat in adults with Fabry Disease receiving Enzyme Replacement Therapy (ERT).
The secondary objectives were to investigate the effects of lucerastat on plasma and urine levels of biomarkers, to assess its effects on renal and cardiac functions and to determine the pharmacokinetic profile of lucerastat at steady-state.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Signed informed consent form
- •Male and female adult subjects with a diagnosis of Fabry Disease (FD) based on historical assessments (residual α-GAL A activity level below lower limit of normal for males and presence of a galactosidase alpha mutation for females) and a history of clinical symptoms of FD
- •On ERT for at least 24 months without any change in dose within the last 6 months prior to screening
排除标准
- •Severe renal function impairment
- •Severe residual neurologic deficit
- •Clinically significant unstable cardiac disease
- •Any circumstances or conditions, which, in the opinion of the investigator, may have affected full participation in the study or compliance with the protocol
研究组 & 干预措施
Lucerastat group
Ten subjects with Fabry Disease received 1000 mg of oral lucerastat twice daily for 12 weeks in addition to their standard of care treatment (enzyme replace therapy).
干预措施: Lucerastat (Drug)
Lucerastat group
Ten subjects with Fabry Disease received 1000 mg of oral lucerastat twice daily for 12 weeks in addition to their standard of care treatment (enzyme replace therapy).
干预措施: Enzyme replacement therapy (ERT) (Drug)
Control group
Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group.
干预措施: Enzyme replacement therapy (ERT) (Drug)
结局指标
主要结局
Number of subjects with treatment-emergent adverse events and serious adverse events
时间窗: Up to Week 12
Change from baseline in blood pressure
时间窗: Up to Week 12
Change from baseline in heart rate
时间窗: Up to Week 12
Change from baseline in electrocardiogram (ECG) variables
时间窗: Up to Week 12
The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG
Change from baseline in body weight
时间窗: Up to Week 12
Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
时间窗: Up to Week 12
Number of subjects with treatment-emergent abnormalities in laboratory variables
时间窗: Up to Week 12
次要结局
- Change from baseline in estimated glomerular filtration rate (eGFR)(Up to Week 12)
- Change from baseline in urine albumin-to-creatinine ratio (UACR)(Up to Week 12)
- Terminal half-life [t(1/2)]of lucerastat(At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose)
- Change from baseline in plasma biomarkers of Fabry Disease(Up to Week 12)
- Change from baseline in left ventricular ejection fraction (LVEF)(Up to Week 12)
- Time to reach Cmax (tmax) of lucerastat(At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose)
- Change from baseline in urine biomarker of Fabry Disease(Up to Week 12)
- Change from baseline in left ventricular mass index (LVMi)(Up to Week 12)
- Maximum plasma concentration (Cmax) of lucerastat(At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose)
- Area under the plasma concentration-time curve [AUC(tau)] of lucerastat(At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose)