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. Issue 4 (22nd December 2014)

• Record Type: Journal Article
• Authors: Johnson, Franklin K.; Mudd, Paul N.; DiMino, Tara; Vosk, Jennie; Sitaraman, Sheela; Boudes, Pol; France, Nicholas; Barlow, Carrolee
• Is Part Of: Clinical pharmacology in drug development. Volume 4:Issue 4(2015:Jul./Aug.)
• Page Start: 256
• Page End: 261
• Publication Date: 2014-12-22
• Subjects: Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.149
• Languages: English
• ISSNs: 2160-7648

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="cpdd149-sec-0001" sec-type="section"> <title>Objectives</title> <p>Renal function may progressively decline in patients with Fabry disease. This study assessed pharmacokinetics, safety, and tolerability of a single oral dose of migalastat HCl 150 mg in subjects with normal or mildly, moderately, or severely impaired renal function.</p> </sec> <sec id="cpdd149-sec-0002" sec-type="section"> <title>Methods</title> <p>Volunteers were enrolled into two cohorts stratified for renal function calculated using the Cockcroft–Gault equation for creatinine clearance. Pharmacokinetic parameters determined were: area under the concentration–time curve (AUC) from time zero to the last measurable concentration postdose (AUC<sub>0–t</sub>) and extrapolated to infinity (AUC<sub>0–∞</sub>), maximum observed concentration (C<sub>max</sub>), time to C<sub>max</sub> (t<sub>max</sub>), concentration at 48 hours postdose (C<sub>48h</sub>), terminal elimination half‐life (t<sub>1/2</sub>), oral clearance (CL/F), and apparent terminal elimination rate constant (λz) (<ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> registration: NCT01730469).</p> </sec> <sec id="cpdd149-sec-0003" sec-type="section"> <title>Results</title> <p>Thirty‐two subjects enrolled and completed the study (Cohort 1: n = 24; Cohort 2: n = 8). Migalastat clearance decreased with increasing renal impairment, resulting in increases in migalastat HCl plasma t<sub>1/2</sub>, AUC<sub>0–∞</sub>, and C<sub>48h</sub> compared with subjects with normal renal function. Incidence of adverse events was comparable across all renal function groups.</p> </sec> <sec id="cpdd149-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Plasma migalastat clearance decreased as degree of renal impairment increased. Data from the migalastat HCl clinical program will guide dosing and intervals for patients with Fabry disease with renal impairment.</p> </sec> </abstract>