Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia.
negative symptoms
schizophrenia
treatment
Journal
Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760
Informations de publication
Date de publication:
07 05 2022
07 05 2022
Historique:
pubmed:
26
2
2022
medline:
11
5
2022
entrez:
25
2
2022
Statut:
ppublish
Résumé
This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population. Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score. NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P ≤ .064), but reached nominal significance (P ≤ .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P ≤ .021 and P ≤ .017, respectively). Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.
Sections du résumé
BACKGROUND
This is a placebo-controlled multi-national trial of roluperidone, a compound with antagonist properties for 5-HT2A, sigma2, and α1A-adrenergic receptors, targeting negative symptoms in patients with schizophrenia. This trial follows a previous trial that demonstrated roluperidone superiority over placebo in a similar patient population.
METHODS
Roluperidone 32 mg/day, roluperidone 64 mg/day, or placebo was administered for 12 weeks to 513 patients with schizophrenia with moderate to severe negative symptoms. The primary endpoint was the PANSS-derived Negative Symptom Factor Score (NSFS) and the key secondary endpoint was Personal and Social Performance scale (PSP) total score.
RESULTS
NSFS scores were lower (improved) for roluperidone 64 mg compared to placebo and marginally missing statistical significance for the intent-to-treat (ITT) analysis data set (P ≤ .064), but reached nominal significance (P ≤ .044) for the modified-ITT (m-ITT) data set. Changes in PSP total score were statistically significantly better on roluperidone 64 mg compared to placebo for both ITT and m-ITT (P ≤ .021 and P ≤ .017, respectively).
CONCLUSIONS
Results of this trial confirm the potential of roluperidone as a treatment of negative symptoms and improving everyday functioning in patients with schizophrenia. Study registration: Eudra-CT: 2017-003333-29; NCT03397134.
Identifiants
pubmed: 35211743
pii: 6536645
doi: 10.1093/schbul/sbac013
pmc: PMC9077422
doi:
Substances chimiques
Antipsychotic Agents
0
Indoles
0
roluperidone
4P31I0M3BF
Banques de données
ClinicalTrials.gov
['NCT03397134']
EudraCT
['2017-003333-29']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
609-619Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
Références
Schizophr Res. 2018 Jul;197:269-273
pubmed: 29275856
Biol Psychiatry. 2017 Jul 1;82(1):8-16
pubmed: 28117049
Eur Neuropsychopharmacol. 2014 May;24(5):645-92
pubmed: 24820238
Dialogues Clin Neurosci. 2018 Sep;20(3):215-221
pubmed: 30581291
Eur Psychiatry. 2000 Aug;15(5):321-9
pubmed: 11032464
Pharmaceuticals (Basel). 2011;4(6):880-914
pubmed: 21904468
Psychol Med. 2014 Oct;44(14):3007-16
pubmed: 25066792
J Clin Psychiatry. 2010 Mar;71(3):280-6
pubmed: 19895779
Rev Neurosci. 2018 Sep 25;29(7):727-744
pubmed: 29573379
Br J Psychiatry. 2016 Nov;209(5):361-365
pubmed: 27802977
Schizophr Res. 2019 Sep;211:103-104
pubmed: 31375316
Curr Pharm Des. 2012;18(7):863-74
pubmed: 22288408
Clin Psychol Sci. 2020 May 1;8(3):555-568
pubmed: 33758684
Neuropsychopharmacology. 2019 Oct;44(11):1955-1966
pubmed: 31212302
Front Pharmacol. 2020 Sep 29;11:581098
pubmed: 33117176
Schizophr Bull. 2021 Jan 23;47(1):44-53
pubmed: 32467967
Eur Neuropsychopharmacol. 2014 Oct;24(10):1615-21
pubmed: 25172269
JAMA Psychiatry. 2013 Sep;70(9):898-900
pubmed: 23824206
NPJ Schizophr. 2021 Feb 26;7(1):16
pubmed: 33637748
Front Neurosci. 2021 Jan 20;14:600178
pubmed: 33551724
Innov Clin Neurosci. 2017 Dec 1;14(11-12):30-40
pubmed: 29410935
Psychopathology. 1997;30(5):263-74
pubmed: 9353855
Acta Psychiatr Scand. 2007 Dec;116(6):403-18
pubmed: 17941964
Lancet Psychiatry. 2018 Aug;5(8):664-677
pubmed: 29602739
Schizophr Bull. 2020 Jul 8;46(4):964-970
pubmed: 31989151
Curr Neuropharmacol. 2005 Oct;3(4):267-80
pubmed: 18369400
Synapse. 2014 Feb;68(2):73-84
pubmed: 24123353
J Comp Eff Res. 2017 Nov;6(8):639-648
pubmed: 28511548
Schizophr Res. 2019 Apr;206:355-361
pubmed: 30482643
Int J Mol Sci. 2021 Apr 25;22(9):
pubmed: 33922888
Schizophr Res. 2020 Jun;220:232-239
pubmed: 32201031
Schizophr Bull. 2017 Jul 1;43(4):712-719
pubmed: 28969356
Biometrics. 1997 Sep;53(3):983-97
pubmed: 9333350
Schizophr Res. 2014 Dec;160(1-3):136-41
pubmed: 25468184
Am J Psychiatry. 2017 Dec 1;174(12):1195-1202
pubmed: 28750582
JAMA Psychiatry. 2013 Sep;70(9):913-20
pubmed: 23824214
Innov Clin Neurosci. 2017 Dec 1;14(11-12):18-22
pubmed: 29410933
J Clin Psychiatry. 2014;75 Suppl 1:3-7
pubmed: 24581452
Lancet. 2017 Mar 18;389(10074):1077-1078
pubmed: 28185671
Schizophr Bull. 2011 Mar;37(2):291-9
pubmed: 20861151
Dialogues Clin Neurosci. 2020 Mar;22(1):81-85
pubmed: 32699508
J Pharmacol Exp Ther. 2000 Mar;292(3):900-11
pubmed: 10688603