A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease
- Conditions
- Fabry Disease
- Interventions
- Drug: Enzyme replacement therapy (ERT)
- Registration Number
- NCT02930655
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lucerastat group Lucerastat 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). Lucerastat group Enzyme replacement therapy (ERT) 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). Control group Enzyme replacement therapy (ERT) Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group.
- Primary Outcome Measures
Name Time Method Change from baseline in blood pressure Up to Week 12 Change from baseline in heart rate Up to Week 12 Change from baseline in electrocardiogram (ECG) variables 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 Up to Week 12 Number of subjects with treatment-emergent adverse events and serious adverse events Up to Week 12 Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT Up to Week 12 Number of subjects with treatment-emergent abnormalities in laboratory variables Up to Week 12
- Secondary Outcome Measures
Name Time Method Change from baseline in urine albumin-to-creatinine ratio (UACR) Up to Week 12 UACR was used to monitor renal function in subjects with Fabry Disease
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 left ventricular ejection fraction (LVEF) Up to Week 12 LVEF was used to monitor cardiac function in subjects with Fabry Disease
Change from baseline in estimated glomerular filtration rate (eGFR) Up to Week 12 eGFR was used to monitor renal function in subjects with Fabry Disease
Change from baseline in plasma biomarkers of Fabry Disease Up to Week 12 Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
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 tmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Change from baseline in urine biomarker of Fabry Disease Up to Week 12 Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
Change from baseline in left ventricular mass index (LVMi) Up to Week 12 LVMi was used to monitor cardiac function in subjects with Fabry Disease
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 Cmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
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 AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours)
Trial Locations
- Locations (1)
Investigator Site
🇩🇪Würzburg, Germany