Cargando…
The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome
OBJECTIVE: To evaluate safety and tolerability and exploratory efficacy end points for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS). METHODS: Gaboxadol is a highly selective orthosteric agonist that activates δ-subunit–containing extrasynaptic γ-aminobutyric aci...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055330/ https://www.ncbi.nlm.nih.gov/pubmed/33443117 http://dx.doi.org/10.1212/WNL.0000000000011409 |
_version_ | 1783680428583944192 |
---|---|
author | Bird, Lynne M. Ochoa-Lubinoff, Cesar Tan, Wen-Hann Heimer, Gali Melmed, Raun D. Rakhit, Amit Visootsak, Jeannie During, Matthew J. Holcroft, Christina Burdine, Rebecca D. Kolevzon, Alexander Thibert, Ronald L. |
author_facet | Bird, Lynne M. Ochoa-Lubinoff, Cesar Tan, Wen-Hann Heimer, Gali Melmed, Raun D. Rakhit, Amit Visootsak, Jeannie During, Matthew J. Holcroft, Christina Burdine, Rebecca D. Kolevzon, Alexander Thibert, Ronald L. |
author_sort | Bird, Lynne M. |
collection | PubMed |
description | OBJECTIVE: To evaluate safety and tolerability and exploratory efficacy end points for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS). METHODS: Gaboxadol is a highly selective orthosteric agonist that activates δ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABA(A)) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd), gaboxadol 10 mg morning dose and 15 mg evening dose (bid), or placebo morning and evening dose. Safety and tolerability were monitored throughout the study. Prespecified exploratory efficacy end points included adapted Clinical Global Impression–Severity and Clinical Global Impression–Improvement (CGI-I) scales, which documented the clinical severity at baseline and change after treatment, respectively. RESULTS: Eighty-eight individuals were randomized. Of 87 individuals (aged 13–45 years) who received at least 1 dose of study drug, 78 (90%) completed the study. Most adverse events (AEs) were mild to moderate, and no life-threatening AEs were reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006). CONCLUSION: After 12 weeks of treatment, gaboxadol was found to be generally well-tolerated with a favorable safety profile. The efficacy as measured by the AS-adapted CGI-I scale warrants further studies. CLINICALTRIALS.GOV IDENTIFIER: NCT02996305. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for individuals with AS, gaboxadol is generally safe and well-tolerated. |
format | Online Article Text |
id | pubmed-8055330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-80553302021-04-20 The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome Bird, Lynne M. Ochoa-Lubinoff, Cesar Tan, Wen-Hann Heimer, Gali Melmed, Raun D. Rakhit, Amit Visootsak, Jeannie During, Matthew J. Holcroft, Christina Burdine, Rebecca D. Kolevzon, Alexander Thibert, Ronald L. Neurology Article OBJECTIVE: To evaluate safety and tolerability and exploratory efficacy end points for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS). METHODS: Gaboxadol is a highly selective orthosteric agonist that activates δ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABA(A)) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd), gaboxadol 10 mg morning dose and 15 mg evening dose (bid), or placebo morning and evening dose. Safety and tolerability were monitored throughout the study. Prespecified exploratory efficacy end points included adapted Clinical Global Impression–Severity and Clinical Global Impression–Improvement (CGI-I) scales, which documented the clinical severity at baseline and change after treatment, respectively. RESULTS: Eighty-eight individuals were randomized. Of 87 individuals (aged 13–45 years) who received at least 1 dose of study drug, 78 (90%) completed the study. Most adverse events (AEs) were mild to moderate, and no life-threatening AEs were reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006). CONCLUSION: After 12 weeks of treatment, gaboxadol was found to be generally well-tolerated with a favorable safety profile. The efficacy as measured by the AS-adapted CGI-I scale warrants further studies. CLINICALTRIALS.GOV IDENTIFIER: NCT02996305. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for individuals with AS, gaboxadol is generally safe and well-tolerated. Lippincott Williams & Wilkins 2021-02-16 /pmc/articles/PMC8055330/ /pubmed/33443117 http://dx.doi.org/10.1212/WNL.0000000000011409 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Article Bird, Lynne M. Ochoa-Lubinoff, Cesar Tan, Wen-Hann Heimer, Gali Melmed, Raun D. Rakhit, Amit Visootsak, Jeannie During, Matthew J. Holcroft, Christina Burdine, Rebecca D. Kolevzon, Alexander Thibert, Ronald L. The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title | The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title_full | The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title_fullStr | The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title_full_unstemmed | The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title_short | The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome |
title_sort | stars phase 2 study: a randomized controlled trial of gaboxadol in angelman syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055330/ https://www.ncbi.nlm.nih.gov/pubmed/33443117 http://dx.doi.org/10.1212/WNL.0000000000011409 |
work_keys_str_mv | AT birdlynnem thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT ochoalubinoffcesar thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT tanwenhann thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT heimergali thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT melmedraund thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT rakhitamit thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT visootsakjeannie thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT duringmatthewj thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT holcroftchristina thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT burdinerebeccad thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT kolevzonalexander thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT thibertronaldl thestarsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT birdlynnem starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT ochoalubinoffcesar starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT tanwenhann starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT heimergali starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT melmedraund starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT rakhitamit starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT visootsakjeannie starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT duringmatthewj starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT holcroftchristina starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT burdinerebeccad starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT kolevzonalexander starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome AT thibertronaldl starsphase2studyarandomizedcontrolledtrialofgaboxadolinangelmansyndrome |