A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease

Fabry Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02930655
• Other study ID #: AC-069-104
• Status: Completed
• Phase: Phase 1
• Start date: February 1, 2015
• Est. completion date: February 1, 2016

Study information

• Verified date: July 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 1, 2016
• Est. primary completion date: February 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent form

• Male and female adult subjects with a diagnosis of Fabry Disease (FD) based on historical assessments (residual a-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

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Drug:
• Lucerastat
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.
• Enzyme replacement therapy (ERT)
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.

Locations

Country	Name	City	State
Germany	Investigator Site	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in blood pressure		Up to Week 12
Primary	Change from baseline in heart rate		Up to Week 12
Primary	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
Primary	Change from baseline in body weight		Up to Week 12
Primary	Number of subjects with treatment-emergent adverse events and serious adverse events		Up to Week 12
Primary	Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT		Up to Week 12
Primary	Number of subjects with treatment-emergent abnormalities in laboratory variables		Up to Week 12
Secondary	Change from baseline in plasma biomarkers of Fabry Disease	Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)	Up to Week 12
Secondary	Change from baseline in urine biomarker of Fabry Disease	Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)	Up to Week 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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