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

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ClinicalTrials.gov Identifier: NCT02930655
Recruitment Status : Completed
First Posted : October 12, 2016
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Tracking Information
First Submitted Date  ICMJE October 10, 2016
First Posted Date  ICMJE October 12, 2016
Last Update Posted Date July 10, 2018
Actual Study Start Date  ICMJE February 1, 2015
Actual Primary Completion Date February 1, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 10, 2016)
  • Change from baseline in blood pressure [ Time Frame: Up to Week 12 ]
  • Change from baseline in heart rate [ Time Frame: Up to Week 12 ]
  • Change from baseline in electrocardiogram (ECG) variables [ Time Frame: 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 [ Time Frame: Up to Week 12 ]
  • Number of subjects with treatment-emergent adverse events and serious adverse events [ Time Frame: Up to Week 12 ]
  • Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT [ Time Frame: Up to Week 12 ]
  • Number of subjects with treatment-emergent abnormalities in laboratory variables [ Time Frame: Up to Week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02930655 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
  • Change from baseline in plasma biomarkers of Fabry Disease [ Time Frame: Up to Week 12 ]
    Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
  • Change from baseline in urine biomarker of Fabry Disease [ Time Frame: Up to Week 12 ]
    Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
  • Change from baseline in left ventricular ejection fraction (LVEF) [ Time Frame: Up to Week 12 ]
    LVEF was used to monitor cardiac function in subjects with Fabry Disease
  • Change from baseline in left ventricular mass index (LVMi) [ Time Frame: Up to Week 12 ]
    LVMi was used to monitor cardiac function in subjects with Fabry Disease
  • Change from baseline in estimated glomerular filtration rate (eGFR) [ Time Frame: Up to Week 12 ]
    eGFR was used to monitor renal function in subjects with Fabry Disease
  • Change from baseline in urine albumin-to-creatinine ratio (UACR) [ Time Frame: Up to Week 12 ]
    UACR was used to monitor renal function in subjects with Fabry Disease
  • Maximum plasma concentration (Cmax) of lucerastat [ Time Frame: 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
  • Time to reach Cmax (tmax) of lucerastat [ Time Frame: 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
  • Area under the plasma concentration-time curve [AUC(tau)] of lucerastat [ Time Frame: 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)
  • Terminal half-life [t(1/2)]of lucerastat [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2016)
  • Change from baseline in plasma biomarkers of Fabry Disease [ Time Frame: Up to Week 12 ]
    Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
  • Change from baseline in urine biomarker of Fabry Disease [ Time Frame: Up to Week 12 ]
    Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
  • Change from baseline in left ventricular ejection fraction (LVEF) [ Time Frame: Up to Week 12 ]
    LVEF was used to monitor cardiac function in subjects with Fabry Disease
  • Change from baseline in left ventricular mass index (LVMi) [ Time Frame: Up to Week 12 ]
    LVMi was used to monitor cardiac function in subjects with Fabry Disease
  • Change from baseline in estimated glomerular filtration rate (eGFR) [ Time Frame: Up to Week 12 ]
    eGFR was used to monitor renal function in subjects with Fabry Disease
  • Change from baseline in urine albumin-to-creatinine ratio (UACR) [ Time Frame: Up to Week 12 ]
    UACR was used to monitor renal function in subjects with Fabry Disease
  • Maximum plasma concentration (Cmax) of lucerastat [ Time Frame: At Week 4 ]
  • Tme to reach Cmax (tmax) of lucerastat [ Time Frame: At Week 4 ]
  • Area under the plasma concentration-time curve [AUC(tau)] of lucerastat [ Time Frame: At Week 4 ]
    AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours)
  • Terminal half-life [t(1/2)]of lucerastat [ Time Frame: At Week 4 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE
  • 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.
    Other Name: ACT-434964
  • Drug: 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.
    Other Names:
    • Fabrazyme
    • Replagal
Study Arms  ICMJE
  • Experimental: 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).
    Interventions:
    • Drug: Lucerastat
    • Drug: Enzyme replacement therapy (ERT)
  • Experimental: Control group
    Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group.
    Intervention: Drug: Enzyme replacement therapy (ERT)
Publications * Guérard 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2016)
14
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 1, 2016
Actual Primary Completion Date February 1, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02930655
Other Study ID Numbers  ICMJE AC-069-104
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Idorsia Pharmaceuticals Ltd.
Study Sponsor  ICMJE Idorsia Pharmaceuticals Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Nicolas Guérard Actelion
PRS Account Idorsia Pharmaceuticals Ltd.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP