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GR181413A/AT1001 (migalastat hydrochloride) is a low molecular weight iminosugar, an analog of the terminal galactose group that is cleaved from the substrate GL-3. This compound was researched and developed as a drug for treatment of Fabry disease. This study, MGM115806, will be the first administration of GR181413A/AT1001 to Japanese subjects to investigate the safety, tolerability and pharmacokinetics of single oral doses in healthy Japanese adult subjects. Approximately 12 subjects will receive three treatments of 50, 150 and 450 mg GR181413A/AT1001 under fasted conditions plus placebo in a dose ascending crossover design. Serial pharmacokinetic samples will be collected and safety assessments will be performed following each dose. The pharmacokinetics and dose proportionality of GR181413A/AT1001 after single oral doses of GR181413A/AT1001 at the dose levels of 50, 150 and 450 mg under fasted conditions will be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 50 mg | Experimental | GR181413A/AT1001 |
|
| 150 mg | Experimental | GR181413A/AT1001 |
|
| 450 mg | Experimental | GR181413A/AT1001 |
|
| Placebo | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GR181413A/AT1001 solution | Drug | Powder for reconstitution |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Profile of plasma pharmacokinetics | AUC, Cmax, tmax, Tlast , t1/2, CL/F, Vz/F | 0, 0.5, 1, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12h post dose |
| Number of Participants with adverse events | up to 24 hr | |
| Change from baseline in clinical laboratory tests (hematology, chemistry and urinalysis) | 0, 24h post dose | |
| Change from baseline in vital signs (blood pressure and heart rate) | 0 ,1 , 2, 3, 4, 5, 6, 24h post dose | |
| Change from baseline in 12-lead ECG | 0, i, 2, 3, 6, 24h post dose | |
| Profile of urine pharmacokinetics | Ae, CLr, %Fx | 0-4, 4-10, 10-12, 12-24h post dose |
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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 |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Randwick | New South Wales | 2031 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27536442 | Derived | Ino H, Takahashi N, Terao T, Mudd PN Jr, Hirama T. Pharmacokinetics, safety, and tolerability following single-dose migalastat hydrochloride (GR181413A/AT1001) in healthy male Japanese subjects. J Drug Assess. 2013 Jul 24;2(1):87-93. doi: 10.3109/21556660.2013.827117. eCollection 2013. |
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| GR181413A/AT1001 capsule |
| Drug |
Size 2, hard gelatin capsule, white opaque / blue opaque |
|
| Potable water | Other | Matched, Size 2, hard gelatin capsule, white opaque/blue opaque |
|
| Placebo capsule | Drug | Solution matched |
|
| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| 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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| ID | Term |
|---|---|
| C090092 | migalastat |
| C525167 | larazotide acetate |
| D060766 | Drinking Water |
| ID | Term |
|---|---|
| D014867 | Water |
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| D001628 | Beverages |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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