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Study objectivesThis post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment.MethodsParticipants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups.ResultsCommon early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity.ConclusionsCommon early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

ObjectivesThis analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d.MethodsIn two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy.ResultsAfter 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was -0.84%, compared with 0.54% for placebo, in participants with OSA; and -0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was -1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, -1.2%; 300 mg, -2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of -2.2% and -1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious.ConclusionsSolriamfetol treatment was associated with decreases in body weight in a dose-related manner.

STUDY OBJECTIVES:Few population-based studies have explored how excessive sleepiness (ES) contributes to burden of illness among patients with obstructive sleep apnea (OSA). METHODS:This study utilized data from the annual, cross-sectional 2016 US National Health and Wellness Survey. Respondents self-reporting an OSA diagnosis were categorized as having ES (Epworth Sleepiness Scale [ESS] score ≥ 11) or not having ES (ESS score < 11). Comorbidities, health-related quality of life (HRQoL), and productivity were examined in three groups: OSA with ES (n = 731), OSA without ES (n = 1,452), and non-OSA controls (n = 86,961). RESULTS:The OSA with ES group had significantly higher proportions of respondents reporting depression (62.4% versus 48.0%), gastroesophageal reflux disease (39.0% versus 29.4%), asthma (26.3% versus 20.7%), and angina (7.8% versus 6.7%) compared to the OSA without ES group (P < .05). After controlling for covariates, the OSA with ES group had significantly lower (worse) scores for mental component score (41.81 versus 45.65 versus 47.81), physical component score (46.62 versus 48.68 versus 51.36), and SF-6D (0.65 versus 0.69 versus 0.73) compared with OSA without ES and non-OSA controls (all P < .001). The OSA with ES group had significantly higher (greater burden) mean rates of presenteeism (25.98% impairment versus 19.24% versus 14.75%), work impairment (29.41% versus 21.82% versus 16.85%), and activity impairment (31.09% versus 25.46% versus 19.93%) compared with OSA without ES and non-OSA controls (all P < .01) after controlling for covariates. CONCLUSIONS:OSA with ES is associated with higher prevalence of comorbidities, reduced HRQoL, and greater impairment in productivity compared to OSA without ES and compared to non-OSA controls.

Joyce S Willens,1 Iwona Bucior,2 Shay Bujanover,2 Neel Mehta3 1Villanova University, Villanova, PA, 2Depomed, Inc., Newark, CA, 3Weill-Cornell Pain Medicine Center, New York, NY, USA Abstract: When used in multimodal analgesia for acute pain, nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the requirement for opioids during the perioperative period. To provide more insight into pain treatment during the outpatient period, we examined the use of opioid rescue medication (RM) and described the relationship between pain intensity and RM use in patients with acute pain after bunionectomy. Patients received placebo or 25 mg of a liquid-filled capsule version of the NSAID diclofenac potassium (DPLFC; n=188 patients/group) every 6 hours during the 48-hour inpatient period through the end of outpatient dosing on day 4. Opioid RM (hydrocodone/acetaminophen tablets, 5 mg/500 mg) was available as needed, but taken at least 1 hour post-study medication. Fewer patients taking DPLFC versus placebo requested opioid RM during the inpatient period (4.8%–44.7% versus 25.0%–90.4%) and also during the outpatient period (3.7%–16.0% versus 13.1%–46.4%). Moderate or severe pain after surgery (P=0.0307 and P=0.0002, respectively) or at second dose (P=0.0006 and P=0.0002, respectively) was predictive of RM use. Patients taking RM (placebo/DPLFC) reported more adverse events (RM 55.7%/40.6%; no RM 29.4%/26.0%). Most adverse events in the RM group were opioid-related. In summary, this study shows that DPLFC lowers the requirement for opioids, which is associated with a reduction in the occurrence of treatment side effects, while maintaining adequate analgesia for patients with moderate acute pain in both the outpatient and outpatient periods. Patients with more severe pain are more likely to use RM, but they still use fewer opioids when treated with DPLFC. This suggests that multimodal treatment using DPLFC and an opioid may offer an important