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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lucerastat group | Experimental | 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 | Experimental | Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lucerastat | Drug | Hard gelatin capsules for oral administration formulated at a strength of 250 mg, and administered as 4 capsules in the morning and 4 capsules in the evening. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG | Up to Week 12 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in plasma biomarkers of Fabry Disease | Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL) | Up to Week 12 |
| Change from baseline in urine biomarker of Fabry Disease |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolas Guérard | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Würzburg | 97080 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28088251 | Derived | 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. |
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| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
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| ID | Term |
|---|---|
| C090092 | migalastat |
| D056947 | Enzyme Replacement Therapy |
| C459420 | agalsidase beta |
| C000627036 | agalsidase alfa |
| ID | Term |
|---|---|
| D057487 | Enzyme Therapy |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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|
| Enzyme replacement therapy (ERT) | Drug | All the subjects received an ERT as background therapy for at least 24 months prior to the screening visit and they had to continue receiving this treatment during the conduct of the study. |
|
|
Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
| Up to Week 12 |
| Change from baseline in left ventricular ejection fraction (LVEF) | LVEF was used to monitor cardiac function in subjects with Fabry Disease | Up to Week 12 |
| Change from baseline in left ventricular mass index (LVMi) | LVMi was used to monitor cardiac function in subjects with Fabry Disease | Up to Week 12 |
| Change from baseline in estimated glomerular filtration rate (eGFR) | eGFR was used to monitor renal function in subjects with Fabry Disease | Up to Week 12 |
| Change from baseline in urine albumin-to-creatinine ratio (UACR) | UACR was used to monitor renal function in subjects with Fabry Disease | Up to Week 12 |
| Maximum plasma concentration (Cmax) of lucerastat | 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 | 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 |
| Time to reach Cmax (tmax) of lucerastat | 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 | 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 | AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours) | 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 |
| 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 |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |