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Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration
Author(s) -
Klopstock Thomas,
Videnovic Aleksandar,
Bischoff Almut Turid,
Bonnet Cecilia,
Cif Laura,
Comella Cynthia,
CorreaVela Marta,
Escolar Maria L.,
Fraser Jamie L.,
Gonzalez Victoria,
Hermanowicz Neal,
Jech Robert,
Jinnah Hyder A.,
Kmiec Tomasz,
Lang Anthony,
Martí Maria J.,
MercimekAndrews Saadet,
Monduy Migvis,
Nimmo Graeme A.M.,
PerezDueñas Belen,
Pfeiffer Helle Cecilie Viekilde,
Planellas Lluis,
Roze Emmanuel,
Thakur Nivedita,
Tochen Laura,
VanegasArroyave Nora,
Zorzi Giovanna,
Burns Colleen,
Greblikas Feriandas
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28392
Subject(s) - placebo , medicine , randomized controlled trial , adverse effect , clinical endpoint , physical therapy , pathology , alternative medicine
Abstract Background Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods This randomized, double‐blind, placebo‐controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24‐week double‐blind period. Patients with pathogenic variants of PANK2 , aged 6 to 65 years, with a score ≥6 on the PKAN‐Activities of Daily Living (PKAN‐ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN‐ADL. Results Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN‐related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN‐ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment‐emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN‐ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.