An open‐label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function

Johnson, Franklin K.; Mudd, Paul N.; DiMino, Tara; Vosk, Jennie; Sitaraman, Sheela; Boudes, Pol; Barlow, Carrolee

doi:10.1002/cpdd.149

Cited by 13 publications

(10 citation statements)

References 9 publications

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“…Oral migalastat exhibits dose-proportional pharmacokinetics across a dose range of 75–1250 mg [2, 3, 23]. In healthy fasted volunteers, migalastat was rapidly absorbed, reaching maximum plasma concentrations (C max ) within 1–6 h (median 3 h) after a single 123 mg dose [23, 31, 32]. In patients with Fabry disease receiving migalastat 123 mg once every other day for 14 days, C max was attained within an estimated time of 2.6 h (abstract) [33].…”

Section: Pharmacokinetic Properties Of Migalastatmentioning

confidence: 99%

“…In a population pharmacokinetic analysis, the clearance of migalastat did not differ to a clinically relevant extent between patients with Fabry disease aged ≥ 65 years and those aged < 65 years [3]. In non-Fabry patients with renal impairment, exposure to migalastat and t 1/2 increased with increasing degrees of renal impairment (mild, moderate and severe renal impairment were associated with 1.2-, 1.8- and 4.5-fold increases in exposure relatively to healthy controls, respectively; t 1/2 was 7.7, 22.2 and 32.3 h, respectively) [31]. The use of migalastat has not been studied in patients with Fabry disease who have severe renal impairment [2, 3], or who have hepatic impairment; however, hepatic impairment is not expected to affect the pharmacokinetics of migalastat, based on the metabolism and excretion pathways [3].…”

Section: Pharmacokinetic Properties Of Migalastatmentioning

confidence: 99%

See 1 more Smart Citation

Migalastat: A Review in Fabry Disease

McCafferty

Scott

2019

Drugs

128

105

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Fabry disease is a rare lysosomal disorder characterized by deficient or absent α-galactosidase A activity resulting from mutations in the GLA gene. Migalastat (Galafold™), a pharmacological chaperone, stabilizes and facilitates trafficking of amenable mutant forms of α-galactosidase A enzyme from the endoplasmic reticulum to lysosomes and increases its lysosomal activity. Oral migalastat is the first pharmacological chaperone approved for treating patients [aged ≥ 18 years (USA and Canada) or ≥ 16 years in other countries] with Fabry disease who have a migalastat-amenable GLA mutation. In the FACETS trial in enzyme replacement therapy (ERT)-naive patients with GLA mutations amenable or non-amenable to migalastat, there was no significant difference between the migalastat and placebo groups for the proportion of patients achieving a ≥ 50% reduction in the number of globotriaosylceramide (GL-3) inclusions/kidney interstitial capillary (KIC) at 6 months [primary endpoint; intent-to-treat (ITT) population]. In the modified ITT population (i.e. patients with migalastat-amenable GLA mutations), relative to placebo, migalastat treatment significantly reduced the mean number of GL-3 inclusions/KIC and plasma lyso-globotriaosylsphingosine levels at 6 months. Among evaluable patients, migalastat maintained renal function and reduced cardiac mass after ≤ 24 months’ therapy. In the ATTRACT trial in ERT-experienced patients, renal function was maintained during 18 months of migalastat or ERT; however, migalastat significantly reduced cardiac mass compared with ERT. Migalastat was generally well tolerated in both of these trials. Given its convenient oral regimen and the limited therapeutic options available, migalastat is an important treatment option for Fabry disease in patients with migalastat-amenable GLA mutations.

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Section: Pharmacokinetic Properties Of Migalastatmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Migalastatmentioning

confidence: 99%

Migalastat: A Review in Fabry Disease

McCafferty

Scott

2019

Drugs

128

105

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“…The median t max and mean t , but not C max , of migalastat were increased in volunteers with mild, moderate or severe renal impairment compared to volunteers with normal renal function after administration of a single 150 mg oral dose (n = 8 per cohort). Mean AUC ratios increased by 1.2-, 1.9-, and 4.3-fold in volunteers with mild, moderate and severe renal impairment, respectively, compared to volunteers with normal renal function [7].…”

Section: Pharmacokineticsmentioning

confidence: 99%

Migalastat: First Global Approval

Markham

2016

Drugs

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Migalastat (Galafold™)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of α-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations. Fabry disease is a rare disorder that results in a deficiency or absence of α-galactosidase, leading to accumulation of globotriaosylceramide in the lysosomes of various cells. This article summarizes the milestones in the development of migalastat leading to this first approval in the EU for the long-term treatment of adults and adolescents aged ≥16 years with a confirmed diagnosis of Fabry disease.

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“…Migalastat hydrochloride is an analog of the terminal galactose of Gb3 that binds and stabilizes wild type and mutant forms of α-Gal A [114]. In a phase III trial of migalastat a significant and durable reduction in kidney Gb3 levels was seen in migalastat treated patients with amenable mutations [115].…”

Section: Treatment Of Fabry Nephropathymentioning

confidence: 99%