Clinical trial NCT02930655: A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fabry Disease
Keywords: Fabry disease
lucerastat
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2016-10-12
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change from baseline in blood pressure
timeFrame: Up to Week 12
measure: Change from baseline in heart rate
timeFrame: Up to Week 12
measure: Change from baseline in electrocardiogram (ECG) variables
timeFrame: Up to Week 12
measure: Change from baseline in body weight
timeFrame: Up to Week 12
measure: Number of subjects with treatment-emergent adverse events and serious adverse events
timeFrame: Up to Week 12
measure: Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
timeFrame: Up to Week 12
measure: Number of subjects with treatment-emergent abnormalities in laboratory variables
timeFrame: Up to Week 12
Secondary outcomes:
measure: Change from baseline in plasma biomarkers of Fabry Disease
timeFrame: Up to Week 12
measure: Change from baseline in urine biomarker of Fabry Disease
timeFrame: Up to Week 12
measure: Change from baseline in left ventricular ejection fraction (LVEF)
timeFrame: Up to Week 12
measure: Change from baseline in left ventricular mass index (LVMi)
timeFrame: Up to Week 12
measure: Change from baseline in estimated glomerular filtration rate (eGFR)
timeFrame: Up to Week 12
measure: Change from baseline in urine albumin-to-creatinine ratio (UACR)
timeFrame: Up to Week 12
measure: Maximum plasma concentration (Cmax) of lucerastat
timeFrame: 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
measure: Time to reach Cmax (tmax) of lucerastat
timeFrame: 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
measure: Area under the plasma concentration-time curve [AUC(tau)] of lucerastat
timeFrame: 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
measure: Terminal half-life [t(1/2)]of lucerastat
timeFrame: 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
Other outcomes:
Locations:
city: Würzburg
country: Germany
facility: Investigator Site
Study officials:
affiliation: Actelion
name: Nicolas Guérard
role: STUDY_DIRECTOR
References:
citation: Guerard N, Morand O, Dingemanse J. Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects. Orphanet J Rare Dis. 2017 Jan 14;12(1):9. doi: 10.1186/s13023-017-0565-9.