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Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) and how migalastat works in participants with Fabry disease.
This was a Phase 2, open-label study in male participants with Fabry disease. The study consisted of a 4-week screening period during which participants' genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat via an in vitro assay. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat 150 milligrams (mg) once every other day (QOD) for 12 weeks during the treatment period. Participants could then opt to participate in the extension period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Migalastat | Experimental | Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week extension period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| migalastat HCl | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event with a start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Day 1 (after dosing) through Week 48 (end of extension period) |
| Measure | Description | Time Frame |
|---|---|---|
| α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48 | PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat. α-Gal A activity in PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor, Clinical Research | Amicus Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parkville | Australia | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27657681 | Derived | Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22. | |
| 23176611 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Migalastat | Participants received migalastat 150 milligrams (mg) orally every other day (QOD) during the 12-week treatment period and the optional 36-week extension period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period |
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| Extension Period |
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Safety Population: all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Migalastat | Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event with a start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Safety Population: all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Day 1 (after dosing) through Week 48 (end of extension period) |
|
Day 1 after dosing through Week 48 (end of extension period).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Migalastat | Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block | Cardiac disorders | MedDRA 8.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA 8.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Medical Affairs | +1-877-426-4287 (877-4-AMICUS) | MedInfoUSA@amicusrx.com |
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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 |
| C525167 | larazotide acetate |
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| Baseline, Week 12 (end of treatment period), Week 48 (end of extension period) |
| Porto Alegre |
| Brazil |
| Derived |
| Germain DP, Giugliani R, Hughes DA, Mehta A, Nicholls K, Barisoni L, Jennette CJ, Bragat A, Castelli J, Sitaraman S, Lockhart DJ, Boudes PF. Safety and pharmacodynamic effects of a pharmacological chaperone on alpha-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Orphanet J Rare Dis. 2012 Nov 24;7:91. doi: 10.1186/1750-1172-7-91. |
|
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
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| Secondary | α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48 | PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat. α-Gal A activity in PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification. | PD Population: All participants who received at least 1 dose of study drug and had at least 1 non-missing postbaseline PD parameter recorded. Participants who discontinued prior to the specified time point were not analyzed because no data were available. | Posted | Number | nmol 4-MU/hr/mg protein | Baseline, Week 12 (end of treatment period), Week 48 (end of extension period) |
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|
| 1 |
| 4 |
| 3 |
| 4 |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA 8.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 8.0 | Systematic Assessment |
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| Bifascicular block | Cardiac disorders | MedDRA 8.0 | Systematic Assessment |
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| Bundle branch block left | Cardiac disorders | MedDRA 8.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 8.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 8.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 8.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 8.0 | Systematic Assessment |
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| Blood thyroid stimulating hormone increased | Investigations | MedDRA 8.0 | Systematic Assessment |
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| QRS axis abnormal | Investigations | MedDRA 8.0 | Systematic Assessment |
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| Venous pressure jugular increased | Investigations | MedDRA 8.0 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Nervousness | Psychiatric disorders | MedDRA 8.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 8.0 | Systematic Assessment |
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| Renal pain | Renal and urinary disorders | MedDRA 8.0 | Systematic Assessment |
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| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA 8.0 | Systematic Assessment |
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| Poor peripheral circulation | Vascular disorders | MedDRA 8.0 | Systematic Assessment |
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The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| 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 |
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| Participant 1 Week 48 |
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| Participant 2 Baseline |
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| Participant 2 Week 12 |
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| Participant 2 Week 48 |
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| Participant 3 Baseline |
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| Participant 3 Week 12 |
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| Participant 3 Week 48 |
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| Participant 4 Baseline |
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| Participant 4 Week 12 |
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| Participant 4 Week 48 |
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