TY - JOUR
T1 - Solriamfetol for the Treatment of Excessive Daytime Sleepiness in Participants with Narcolepsy with and without Cataplexy
T2 - Subgroup Analysis of Efficacy and Safety Data by Cataplexy Status in a Randomized Controlled Trial
AU - Dauvilliers, Yves
AU - Shapiro, Colin
AU - Mayer, Geert
AU - Lammers, Gert Jan
AU - Emsellem, Helene
AU - Plazzi, Giuseppe
AU - Chen, Dan
AU - Carter, Lawrence P.
AU - Lee, Lawrence
AU - Black, Jed
AU - Thorpy, Michael J.
N1 - Funding Information:
Under the direction of the authors, Kirsty Nahm, MD, of The Curry Rockefeller Group, LLC (CRG), and Diane Sloan, PharmD, of Peloton Advantage, LLC, an OPEN Health company, provided medical writing assistance for this manuscript. Editorial assistance was also provided by CRG and Peloton Advantage. Jazz Pharmaceuticals provided funding to CRG and Peloton Advantage for writing and editorial support.
Funding Information:
This clinical research was funded by Jazz Pharmaceuticals (the sponsor), which also took a leadership role in designing the study. All of the authors, including authors from Jazz Pharmaceuticals, assisted in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.
Funding Information:
Yves Dauvilliers has received consultancy fees and/or honoraria and has been a speakers’ bureau member and/or an advisory board participant for UCB Pharma, Bioprojet, Theranexus, Flamel, Harmony Biosciences, Takeda, Idorsia, and Jazz Pharmaceuticals. Colin Shapiro has received research funding from the National Institutes of Health and the Canadian Institutes of Health Research and has served on the speakers’ bureau for Jazz Pharmaceuticals. Geert Mayer has received honoraria from the Paul Ehrlich Institute, Germany; has served on the speakers’ bureau for UCB Pharma, Sanofi, and Bioprojet; and is a board member of the International REM Sleep Behavior Study Group. Gert Jan Lammers has received consultancy fees and/or honoraria and has been a speakers’ bureau member and/or an advisory board participant for UCB Pharma, Bioprojet, Theranexus, and Jazz Pharmaceuticals. Helene Emsellem has received consultancy fees, honoraria, and/or has been a speakers’ bureau member and advisory board participant for Jazz Pharmaceuticals and Vanda Pharmaceuticals; has received research funding from Jazz Pharmaceuticals, Vanda Pharmaceuticals, Eisai, Flamel (Avadel), Balance Therapeutics, Merck & Co, NightBalance, Novartis, Philips Respironics, Idorsia Pharmaceuticals, and Harmony Biosciences; and is a board member of the National Sleep Foundation. Giuseppe Plazzi has participated in advisory boards for UCB, Bioprojet, and Jazz Pharmaceuticals. Dan Chen, Lawrence P. Carter, and Lawrence Lee are employees of Jazz Pharmaceuticals who, in the course of this employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Jed Black is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals plc. Michael J. Thorpy has received research/grant support and consultancy and speakers’ bureau fees from Jazz Pharmaceuticals; research funding from Flamel; consultancy and speakers’ bureau fees from Merck & Co., Inc., and Cephalon, Inc. (now Teva Pharmaceutical Industries, Ltd); and consultancy fees from Harmony Biosciences.
Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Background: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, improved wakefulness and reduced excessive daytime sleepiness (EDS) in studies of participants with narcolepsy with and without cataplexy. Objective: Prespecified subgroup analyses of data from a 12-week randomized, double-blind, placebo-controlled, phase III trial of solriamfetol for EDS in narcolepsy evaluated the efficacy and safety of solriamfetol by cataplexy status. Methods: Participants with narcolepsy received solriamfetol (75, 150, or 300 mg/day) or placebo and were stratified by cataplexy status. Coprimary endpoints were change from baseline on Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS); Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Change in frequency of cataplexy attacks was evaluated in participants reporting cataplexy at baseline. Safety was evaluated. No adjustments were made for multiple comparisons; therefore p values are nominal. Results: There were 117 participants in the cataplexy subgroup and 114 in the non-cataplexy subgroup. At week 12, least-squares (LS) mean (95% confidence interval [CI]) differences from placebo on change from baseline in MWT for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were 1.6 (− 3.6 to 6.9), 6.1 (0.7–11.4), and 8.9 (3.5–14.2) minutes, respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup were 3.4 (− 1.9 to 8.7), 9.1 (3.8–14.3), and 11.2 (5.8–16.6) minutes, respectively (p < 0.001; 150 and 300 mg). At week 12, LS mean (95% CI) differences from placebo on ESS change from baseline for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were − 1.3 (− 3.9 to 1.3), − 3.7 (− 6.4 to − 1.1), and − 4.5 (− 7.1 to − 1.9), respectively (p < 0.01; 150 and 300 mg), and in the non-cataplexy subgroup were − 3.0 (− 5.6 to − 0.4), − 3.7 (− 6.3 to − 1.2), and − 4.9 (− 7.6 to − 2.2), respectively (p < 0.05; all doses). For PGI-C at week 12, the mean percentage difference from placebo (95% CI) for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup was 10% (− 15 to 35), 33% (9–57), and 39% (16–61), respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup was 48% (25–70), 44% (21–67), and 52% (30–73), respectively (p < 0.001; all doses), with somewhat differential treatment effects for 75 mg by cataplexy status. No changes in the number of cataplexy attacks were observed for solriamfetol compared with placebo (mean ± standard deviation changes: − 3.6 ± 13.3 [combined solriamfetol] and − 3.5 ± 9.8 [placebo]). Common adverse events (headache, nausea, decreased appetite, and nasopharyngitis) were similar between cataplexy subgroups. Conclusions: These data strongly indicate that solriamfetol was effective in treating EDS in participants with narcolepsy with or without cataplexy, as indicated by robust effects on MWT, ESS, and PGI-C. The safety profile was similar regardless of cataplexy status. Trial Registration and Date: ClinicalTrials.gov NCT02348593. 28 January 2015.
AB - Background: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, improved wakefulness and reduced excessive daytime sleepiness (EDS) in studies of participants with narcolepsy with and without cataplexy. Objective: Prespecified subgroup analyses of data from a 12-week randomized, double-blind, placebo-controlled, phase III trial of solriamfetol for EDS in narcolepsy evaluated the efficacy and safety of solriamfetol by cataplexy status. Methods: Participants with narcolepsy received solriamfetol (75, 150, or 300 mg/day) or placebo and were stratified by cataplexy status. Coprimary endpoints were change from baseline on Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS); Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Change in frequency of cataplexy attacks was evaluated in participants reporting cataplexy at baseline. Safety was evaluated. No adjustments were made for multiple comparisons; therefore p values are nominal. Results: There were 117 participants in the cataplexy subgroup and 114 in the non-cataplexy subgroup. At week 12, least-squares (LS) mean (95% confidence interval [CI]) differences from placebo on change from baseline in MWT for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were 1.6 (− 3.6 to 6.9), 6.1 (0.7–11.4), and 8.9 (3.5–14.2) minutes, respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup were 3.4 (− 1.9 to 8.7), 9.1 (3.8–14.3), and 11.2 (5.8–16.6) minutes, respectively (p < 0.001; 150 and 300 mg). At week 12, LS mean (95% CI) differences from placebo on ESS change from baseline for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup were − 1.3 (− 3.9 to 1.3), − 3.7 (− 6.4 to − 1.1), and − 4.5 (− 7.1 to − 1.9), respectively (p < 0.01; 150 and 300 mg), and in the non-cataplexy subgroup were − 3.0 (− 5.6 to − 0.4), − 3.7 (− 6.3 to − 1.2), and − 4.9 (− 7.6 to − 2.2), respectively (p < 0.05; all doses). For PGI-C at week 12, the mean percentage difference from placebo (95% CI) for solriamfetol 75, 150, and 300 mg in the cataplexy subgroup was 10% (− 15 to 35), 33% (9–57), and 39% (16–61), respectively (p < 0.05; 150 and 300 mg), and in the non-cataplexy subgroup was 48% (25–70), 44% (21–67), and 52% (30–73), respectively (p < 0.001; all doses), with somewhat differential treatment effects for 75 mg by cataplexy status. No changes in the number of cataplexy attacks were observed for solriamfetol compared with placebo (mean ± standard deviation changes: − 3.6 ± 13.3 [combined solriamfetol] and − 3.5 ± 9.8 [placebo]). Common adverse events (headache, nausea, decreased appetite, and nasopharyngitis) were similar between cataplexy subgroups. Conclusions: These data strongly indicate that solriamfetol was effective in treating EDS in participants with narcolepsy with or without cataplexy, as indicated by robust effects on MWT, ESS, and PGI-C. The safety profile was similar regardless of cataplexy status. Trial Registration and Date: ClinicalTrials.gov NCT02348593. 28 January 2015.
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U2 - 10.1007/s40263-020-00744-2
DO - 10.1007/s40263-020-00744-2
M3 - Article
C2 - 32588401
AN - SCOPUS:85086859118
SN - 1172-7047
VL - 34
SP - 773
EP - 784
JO - CNS Drugs
JF - CNS Drugs
IS - 7
ER -
