Richard K Bogan1, Thomas Roth2, Jonathan Schwartz3, Maja Miloslavsky4. 1. University of South Carolina School of Medicine, Columbia, SC. 2. Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI. 3. University of Oklahoma Health Services Center, Oklahoma City, OK. 4. Jazz Pharmaceuticals, Inc., Palo Alto, CA.
Abstract
STUDY OBJECTIVES: This post hoc analysis evaluated the time to response that can be expected with sodium oxybate (SXB) for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy. METHODS: Data were from a 4-week, double-blind, randomized, placebo-controlled trial (GHB-2; N = 136) of oral SXB 3 g, 6 g, and 9 g nightly, and its 12-month open-label extension (GHB-3). Two response definitions were utilized: ≥ 20% improvement in Epworth Sleepiness Scale (ESS) score (EDS responders), and ≥ 50% reduction in weekly cataplexy attacks (cataplexy responders). These thresholds were previously determined to be clinically relevant based on analysis of the relationship of Clinical Global Impression of Change with ESS and number of cataplexy attacks. Kaplan-Meier curves and median times to first response, based on above criteria, and to maximum response were estimated. RESULTS: Among 86 patients randomized toSXB in GHB-2 and continued into GHB-3, 77.6% and 90.7% were EDS and cataplexy responders, respectively. The median (95% CI) times to first response were 37 (31-50) days for EDS and 25 (17-29) days for cataplexy, and median times to maximum response were 106 (85-164) days for EDS and 213 (94-279) days for cataplexy. GHB-3 results among 31 patients initially randomized toplacebo were consistent with those treated with SXB throughout, but with longer times to maximum response. CONCLUSIONS: Response onset, assessed as clinically meaningful improvements in EDS and cataplexy, was observed in most patients within 2 months; a longer period is needed to achieve maximum response. Clinicians should recognize that time to initial and maximum response may take weeks to months.
RCT Entities:
STUDY OBJECTIVES: This post hoc analysis evaluated the time to response that can be expected with sodium oxybate (SXB) for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy. METHODS: Data were from a 4-week, double-blind, randomized, placebo-controlled trial (GHB-2; N = 136) of oral SXB 3 g, 6 g, and 9 g nightly, and its 12-month open-label extension (GHB-3). Two response definitions were utilized: ≥ 20% improvement in Epworth Sleepiness Scale (ESS) score (EDS responders), and ≥ 50% reduction in weekly cataplexy attacks (cataplexy responders). These thresholds were previously determined to be clinically relevant based on analysis of the relationship of Clinical Global Impression of Change with ESS and number of cataplexy attacks. Kaplan-Meier curves and median times to first response, based on above criteria, and to maximum response were estimated. RESULTS: Among 86 patients randomized to SXB in GHB-2 and continued into GHB-3, 77.6% and 90.7% were EDS and cataplexy responders, respectively. The median (95% CI) times to first response were 37 (31-50) days for EDS and 25 (17-29) days for cataplexy, and median times to maximum response were 106 (85-164) days for EDS and 213 (94-279) days for cataplexy. GHB-3 results among 31 patients initially randomized to placebo were consistent with those treated with SXB throughout, but with longer times to maximum response. CONCLUSIONS: Response onset, assessed as clinically meaningful improvements in EDS and cataplexy, was observed in most patients within 2 months; a longer period is needed to achieve maximum response. Clinicians should recognize that time to initial and maximum response may take weeks to months.
Authors: Amy W Amara; Lama M Chahine; Chelsea Caspell-Garcia; Jeffrey D Long; Christopher Coffey; Birgit Högl; Aleksandar Videnovic; Alex Iranzo; Geert Mayer; Nancy Foldvary-Schaefer; Ron Postuma; Wolfgang Oertel; Shirley Lasch; Ken Marek; Tanya Simuni Journal: J Neurol Neurosurg Psychiatry Date: 2017-05-29 Impact factor: 10.154
Authors: Panagis Drakatos; Dimosthenis Lykouras; Grainne D'Ancona; Sean Higgins; Nadia Gildeh; Raluca Macavei; Ivana Rosenzweig; Joerg Steier; Adrian J Williams; Rexford Muza; Brian D Kent; Guy Leschziner Journal: Sleep Med Date: 2017-05-06 Impact factor: 3.492