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Abstract Details

Dose-Regimen Findings for OV101 (Gaboxadol) in Clinical Studies of Angelman Syndrome and Fragile X Syndrome and Implications for Treatment
Child Neurology and Developmental Neurology
Child Neurology and Developmental Neurology Posters (7:00 AM-5:00 PM)
022
To consider the impact of gaboxadol dosing regimens, evaluated in two phase 2 studies of neurodevelopmental disorders, on pharmacodynamic responses and the importance of optimizing dose/regimen for each disorder.
Gaboxadol is a GABA receptor agonist that selectively activates δ-subunit containing extrasynaptic GABAA receptors known to mediate tonic inhibition. Gaboxadol is being actively studied in two neurodevelopmental disorders, Angelman syndrome (AS) and fragile X syndrome (FXS).
STARS was a randomized, placebo-controlled, phase 2 trial enrolling adolescents and adults with molecularly confirmed AS, evaluating safety and exploratory efficacy of gaboxadol at two dosing levels; 15 mg (QD) or 10 mg (morning) plus 15 mg (evening; 25mg total daily dose; BID). ROCKET was a phase 2a randomized dose finding study in FXS evaluating safety with gaboxadol 5 mg QD, BID or TID (5mg, 10mg or 15mg total daily dose). In both studies preliminary efficacy was measured as change from baseline at 12 weeks using the Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scales, completed by the clinician.
Gaboxadol was generally well tolerated at the study doses tested with a safety profile consistent with previous studies. A dosing regimen-related pattern was noted such that improvements in CGI-I at the highest doses (25mg for STARS and 5mg TID for ROCKET) were inferior to those at lower doses (15mg QD for STARS and 5mg QD and BID for ROCKET). CGI-I response rates were 79% and 55% with 15mg QD vs 10/15mg BID, respectively, for AS, and 67%, 72%, and 43% with QD, BID, and TID for FXS. In the STARS study, this translated to a significant improvement vs placebo for the 15mg QD dose but not for the 10/15mg BID regimen.
Optimization of gaboxadol dosing regimen is critical for individualized treatment of neurodevelopmental disorders involving dysfunctional tonic inhibition.
Authors/Disclosures
Elizabeth M. Berry-Kravis, MD, PhD (Rush University Medical Center)
PRESENTER 		The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Zevra. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren.
No disclosure on file
Tom Parry Tom Parry has received personal compensation for serving as an employee of Ovid Therapeutics Inc. Tom Parry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer Ingleheim. Tom Parry has received personal compensation in the range of $0-$499 for serving as a Grant Reviewer with NIH.
No disclosure on file
Alexander Kolevzon Alexander Kolevzon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ovid Therapeutics. Alexander Kolevzon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Alexander Kolevzon has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ovid Therapeutics. Alexander Kolevzon has received stock or an ownership interest from Ovid Therapeutics. The institution of Alexander Kolevzon has received research support from AMO Pharma. Alexander Kolevzon has received publishing royalties from a publication relating to health care.