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@ARTICLE{Klopstock:154280,
author = {Klopstock, Thomas and Videnovic, Aleksandar and Bischoff,
Almut Turid and Bonnet, Cecilia and Cif, Laura and Comella,
Cynthia and Correa-Vela, Marta and Escolar, Maria L and
Fraser, Jamie L and Gonzalez, Victoria and Hermanowicz, Neal
and Jech, Robert and Jinnah, Hyder A and Kmiec, Tomasz and
Lang, Anthony and Martí, Maria J and Mercimek-Andrews,
Saadet and Monduy, Migvis and Nimmo, Graeme A M and
Perez-Dueñas, Belen and Pfeiffer, Helle Cecilie Viekilde
and Planellas, Lluis and Roze, Emmanuel and Thakur, Nivedita
and Tochen, Laura and Vanegas-Arroyave, Nora and Zorzi,
Giovanna and Burns, Colleen and Greblikas, Feriandas},
title = {{F}osmetpantotenate {R}andomized {C}ontrolled {T}rial in
{P}antothenate {K}inase-{A}ssociated {N}eurodegeneration.},
journal = {Movement disorders},
volume = {36},
number = {6},
issn = {1531-8257},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2021-00134},
pages = {1342 - 1352},
year = {2020},
note = {ISSN 1531-8257 not unique: **3 hits**.},
abstract = {Pantothenate kinase-associated neurodegeneration (PKAN)
currently has no approved treatments.The Fosmetpantotenate
Replacement Therapy pivotal trial examined whether treatment
with fosmetpantotenate improves PKAN symptoms and stabilizes
disease progression.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.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.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.},
keywords = {Activities of Daily Living / Double-Blind Method / Humans /
Pantothenate Kinase-Associated Neurodegeneration: drug
therapy / Pantothenate Kinase-Associated Neurodegeneration:
genetics / Pantothenic Acid: analogs $\&$ derivatives /
fosmetpantotenate (Other) / pantothenate kinase-associated
neurodegeneration (Other) / randomized controlled trial
(Other) / treatment (Other)},
cin = {Clinical Dementia Research München},
ddc = {610},
cid = {I:(DE-2719)1111016},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC8246547},
pubmed = {pmid:33200489},
doi = {10.1002/mds.28392},
url = {https://pub.dzne.de/record/154280},
}