Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility.

PURPOSE: Preliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA. METHODS: This trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation. RESULTS: Of 62 patients who were randomized, 60 were included in efficacy analyses. The apnea-hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone (p < .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden (p < .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater Vactive). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine). CONCLUSION: AD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation. TRIAL REGISTRATION: Clinical trial registered with www. CLINICALTRIALS: gov (NCT04445688).

Solriamfetol for Excessive Daytime Sleepiness in Parkinson's Disease: Phase 2 Proof-of-Concept Trial.

BACKGROUND: Solriamfetol is approved (US and EU) for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea. OBJECTIVES: Evaluate solriamfetol safety/efficacy for EDS in Parkinson's disease (PD). METHODS: Phase 2, double-blind, 4-week, crossover trial: adults with PD and EDS were randomized to sequence A (placebo, solriamfetol 75, 150, 300 mg/d), B (solriamfetol 75, 150, 300 mg/d, placebo), or C (placebo). Outcomes (safety/tolerability [primary]; Epworth Sleepiness Scale [ESS]; Maintenance of Wakefulness Test [MWT]) were assessed weekly. P values are nominal. RESULTS: Common adverse events (n = 66): nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), dyspepsia (5.4%). ESS decreased both placebo (-4.78) and solriamfetol (-4.82 to -5.72; P > 0.05). MWT improved dose-dependently with solriamfetol, increasing by 5.05 minutes with 300 mg relative to placebo (P = 0.0098). CONCLUSIONS: Safety/tolerability was consistent with solriamfetol's known profile. There were no significant improvements on ESS; MWT results suggest possible benefit with solriamfetol in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A randomized study of solriamfetol for excessive sleepiness in narcolepsy.

OBJECTIVE: Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy. METHODS: Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI-C) was the key secondary endpoint. RESULTS: Safety and modified intention-to-treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and -6.4 (SE = 0.7) for 300 mg and -5.4 (SE = 0.7) for 150 mg on the ESS versus -1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI-C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%). INTERPRETATION: Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359-370.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.

STUDY OBJECTIVES: Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH. METHODS: Adults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period. RESULTS: Of 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants. CONCLUSIONS: A single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.

Case report: A patient with Delayed Sleep-Wake Phase Disorder and Optic Nerve Hypoplasia treated with tasimelteon: a case study.

We present a case of an adult female diagnosed with Delayed Sleep-Wake Phase Disorder (DSWPD) and Optic Nerve Hypoplasia (ONH), with a confirmed delayed Dim Light Melatonin Onset (DLMO), who reports the inability to fall asleep at their desired bedtime and obtain adequate sleep nightly, despite the ability to have a full night's sleep when not required to be up at a specific time for societal requirements. The participant was enrolled in an 11-month Open-Label Extension (OLE) following the randomized portion of a clinical study and was successfully treated with tasimelteon. DSWPD symptoms were resolved, and their previously delayed sleep-wake cycle was advanced. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04652882, identifier NCT04652882.

Corrigendum: Case report: A patient with Delayed Sleep-Wake Phase Disorder and Optic Nerve Hypoplasia treated with tasimelteon: a case study.

[This corrects the article DOI: 10.3389/fnins.2023.1287514.].

Solriamfetol for the Treatment of Excessive Daytime Sleepiness in Participants with Narcolepsy with and without Cataplexy: Subgroup Analysis of Efficacy and Safety Data by Cataplexy Status in a Randomized Controlled Trial.

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.

Measures of functional outcomes, work productivity, and quality of life from a randomized, phase 3 study of solriamfetol in participants with narcolepsy.

OBJECTIVE: Solriamfetol (formerly JZP-110), a dopamine/norepinephrine reuptake inhibitor, is approved in the US to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy (75-150 mg/d) or obstructive sleep apnea (37.5-150 mg/d). In a randomized, double-blind, placebo-controlled trial in participants with narcolepsy, effects of solriamfetol on functional status, health-related quality of life (HRQoL), and work productivity were evaluated. METHODS: Participants with narcolepsy (N = 239) were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), 36-Item Short Form Health Survey version 2 (SF-36v2), and Work Productivity and Activity Impairment questionnaire for Specific Health Problem (WPAI:SHP). A mixed-effects model with repeated measures was used for comparisons vs placebo. RESULTS: At week 12, solriamfetol increased FOSQ-10 total score, with greatest mean difference from placebo (95% CI) at 300 mg (1.45 [0.31, 2.59]). On SF-36v2, improvements vs placebo were observed in physical component summary scores (300 mg: 2.22 [0.04, 4.41]) and subscales of role physical, general health, and vitality. On WPAI:SHP, solriamfetol 150 mg reduced overall work impairment vs placebo (-15.5 [-29.52, -1.47]), and 150 and 300 mg reduced activity impairment vs placebo (-10.05 [-19.48, -0.62] and -13.49 [-23.19, -3.78], respectively). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Common TEAEs were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. CONCLUSIONS: Solriamfetol improved measures of functional status, HRQoL, and work productivity, particularly at the 150- and 300-mg doses. Most TEAEs were mild to moderate. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02348593, EudraCT number 2014-005487-15.

NightBalance Sleep Position Treatment Device Versus Auto-Adjusting Positive Airway Pressure for Treatment of Positional Obstructive Sleep Apnea.

STUDY OBJECTIVES: Compare treatment efficacy and objective adherence between the NightBalance sleep position treatment (SPT) device and auto-adjusting positive airway pressure (APAP) in patients with exclusive positional obstructive sleep apnea (ePOSA) defined as a supine apnea-hypopnea index (sAHI) ≥ 2 times the nonsupine AHI (nsAHI) and a nsAHI < 10 events/h. METHODS: This prospective multicenter randomized crossover trial enrolled treatment naive participants with ePOSA (AHI ≥ 15 events/h and nsAHI < 10 events/h) or (AHI > 10 and < 15 events/h with daytime sleepiness and nsAH < 5 events/h). Polysomnography and objective adherence determination (device data) were performed at the end of each 6-week treatment. Patient device preference was determined at the end of the study. RESULTS: A total of 117 participants were randomized (58 SPT first, 59 APAP first). Of these, 112 started treatment with the second device (adherence cohort) and 110 completed the study (AHI cohort). The AHI on SPT was higher (mean ± standard deviation, 7.29 ± 6.8 versus 3.71 ± 5.1 events/h, P < .001). The mean AHI difference (SPT-APAP) was 3.58 events/h with a one sided 95% confidence interval upper bound of 4.96 events/h (< the prestudy noninferiority margin of 5 events/h). The average nightly adherence (all nights) was greater on SPT (345.3 ± 111.22 versus 286.98 ± 128.9 minutes, P < .0001). Participants found the SPT to be more comfortable and easier to use and 53% reported a preference for SPT assuming both devices were equally effective. CONCLUSIONS: Treatment with SPT resulted in non-inferior treatment efficacy and greater adherence compared to APAP in ePOSA suggesting that SPT is an effective treatment for this group. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: The POSAtive Study: Study for the Treatment of Positional Obstructive Sleep Apnea; Identifier: NCT03061071; URL: https://clinicaltrials.gov/ct2/show/NCT03061071.

Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in patients with narcolepsy participating in two clinical trials of sodium oxybate.

BACKGROUND: In evaluating pathologic sleepiness, the Epworth Sleepiness Scale (ESS) assesses subjective sleep propensity; the Maintenance of Wakefulness Test (MWT) is an objective measure of the ability to stay awake. This analysis evaluated the strength of the correlation between ESS and MWT with regard to absolute values in scores. METHODS: Data were analyzed separately from the intent-to-treat populations of two eight-week clinical trials of sodium oxybate for the treatment of narcolepsy, SXB-15 and SXB-22. For all treatment groups, correlations between ESS and MWT were evaluated at baseline, week four, and week eight using the Pearson product-moment correlation coefficient. RESULTS: Overall, correlations across all treatment groups in each study described an inverse relationship, reflecting the scoring of each measure (ie, whereas higher ESS scores indicate greater sleepiness, higher MWT scores indicate a greater ability to remain awake). Significant correlations of low-to-moderate strength were observed at all time points in both studies. In SXB-15, correlation coefficients were -0.272, -0.365, and -0.343 at baseline (n = 221), week four (n = 212), and week eight (n = 205), respectively, with all P < 0.0001. Similarly, in SXB-22, correlation coefficients were -0.302 (n = 216), -0.418 (n = 211), and -0.432 (n = 196) at the three time points, respectively, also with all P < 0.0001. CONCLUSION: Although all correlations showed statistical significance, they were of low-to-moderate strength. These results indicate that ESS and MWT measure features of pathologic sleepiness that may be distinct, but partially overlapping. These data corroborate those of other studies, suggesting that physiologic mechanisms that regulate alertness and sleep propensity may function somewhat independently.

Identifying clinically important difference on the Epworth Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110.

BACKGROUND: While scores ≤10 on the Epworth Sleepiness Scale (ESS) are within the normal range, the reduction in elevated ESS score that is clinically meaningful in patients with narcolepsy has not been established. METHODS: This post hoc analysis of a clinical trial of patients with narcolepsy evaluated correlations between Patient Global Impression of Change (PGI-C) and ESS. Data of adult patients with narcolepsy from a double-blind, 12-week placebo-controlled study of JZP-110, a wake-promoting agent, were used in this analysis. Descriptive statistics and receiver operating characteristic (ROC) analysis compared PGI-C (anchor measure) to percent change from baseline in ESS to establish the responder criterion from patients taking either placebo or JZP-110 (treatments). RESULTS: At week 12, patients (n = 10) who reported being "very much improved" on the PGI-C had a mean 76.7% reduction in ESS score, and patients (n = 33) who reported being "much improved" on the PGI-C had a mean 49.1% reduction in ESS score. ROC analysis showed that patients who improved were almost exclusively from JZP-110 treatment group, with an area-under-the-curve of 0.9, and revealed that a 25% reduction in ESS (sensitivity, 81.4%; specificity, 80.9%) may be an appropriate threshold for defining a meaningful patient response to JZP-110 and placebo. CONCLUSIONS: A ≥25% reduction in patients' subjective ESS score may be useful as a threshold to identify patients with narcolepsy who respond to JZP-110 treatment.

Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study.

STUDY OBJECTIVES: To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy. METHODS: This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change. RESULTS: Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%). CONCLUSIONS: At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier NCT01681121.

Sleep Dysfunction and Gastrointestinal Diseases.

Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

Sleep in the modern family: protective family routines for child and adolescent sleep.

STUDY OBJECTIVES: The overall objective of the 2014 National Sleep Foundation Sleep in America Poll "Sleep in the Modern Family" was to obtain a current picture of sleep in families with at least 1 school-aged child. DESIGN: Cross-sectional poll. SETTING: Internet-based interview. PARTICIPANTS: Nationally representative Internet panel of US households with a child 6-17 years. MEASUREMENTS AND RESULTS: Primary measures included parental perception of the importance of sleep, parental and child sleep quality, child sleep duration and habits, technology in bedroom, and family rules. Parents/guardians (n= 1103; mean age, 42; 54% female) completed the survey. Although the majority of parents endorsed the importance of sleep, 90% of children obtain less sleep than recommended. Significant predictors of age-adjusted sufficient sleep duration (estimated conservatively as ≥9 hours for ages 6-11 years and ≥8 hours for ages 12-17 years) included parent education, regular enforcement of rules about caffeine, and whether children left technology on in their bedroom overnight. Significant predictors of excellent sleep quality included whether a bedtime was always enforced and whether children left technology on overnight. CONCLUSIONS: Children generally have better age-appropriate sleep in the presence of household rules and regular sleep-wake routines. Sufficient sleep quantity and adequate sleep quality were protected by well-established rules of sleep hygiene (limited caffeine and regular bedtime). In contrast, sleep deficiency was more likely to be present when parents and children had electronic devices on in the bedroom after bedtime. Public health intervention goals for sleep health might focus on reducing the encroachment of technology and media into time for sleep and supporting well-known sleep hygiene principles.

A 12-week open-label, multicenter study evaluating the safety and patient-reported efficacy of sodium oxybate in patients with narcolepsy and cataplexy.

OBJECTIVE: This study aimed to evaluate safety and efficacy of sodium oxybate (SXB) titrated to effect. METHODS: SXB-naive patients who had participated in a randomized SXB clinical trial and had not been titrated to adequate clinical effect were initiated on open-label SXB at 4.5 g/night and titrated in 1.5-g increments to 6, 7.5, or 9 g/night or down to 3 g/night, based on individual clinical response. Treatment was 12 weeks; safety was the primary outcome. Efficacy was evaluated using the Narcolepsy Symptom Assessment Questionnaire (NSAQ), a five-point scale ("much improved" to "much worse") that assessed changes from baseline in specific symptoms. Response was defined as "much improved" or "somewhat improved" overall at weeks 6 and 12. RESULTS: Of 202 patients, 171 (85%) completed treatment; final doses were 3 g (n = 5), 4.5 g (n = 29), 6 g (n = 80), 7.5 g (n = 66), and 9 g (n = 22). Adverse events (AEs) were reported in 114 patients (56%), serious AEs in five (2%). The most common AEs were nausea (10%), headache (7%), and dizziness (5%). Response rate was 92% at week 6 and 90% at week 12; most patients reported improvements in all individual symptoms. Overall, 60% of patients rated their symptoms at 12 weeks as "much improved," and this improvement was dose dependent. CONCLUSIONS: The SXB safety profile was consistent with parent trials. Ninety percent of patients reported improvements as measured by the NSAQ.

Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy.

BACKGROUND: JZP-110 is a wake-promoting agent with dopaminergic and noradrenergic activity. METHODS: This double-blind, crossover study, randomized adults with narcolepsy with or without cataplexy (N = 33) to placebo or JZP-110 at 150 mg/day (weeks 1 and 3) increased to 300 mg/day (weeks 2 and 4). Patients had to have baseline Epworth Sleepiness Scale (ESS) scores ≥10 and mean sleep latencies ≤10 min on the Maintenance of Wakefulness Test (MWT). Efficacy end points included MWT sleep latency and ESS, and the percentage of patients improved on the Clinical Global Impression of Change. RESULTS: Patients were primarily male (57.6%) and white (69.7%), with a mean (standard deviation) age of 37.1 (12.4) years. At two weeks, the change in the mean MWT sleep latency was 11.8 min longer with JZP-110 than with placebo (P = 0.0002); JZP-110 resulted in greater changes in sleep latency on each MWT trial (P <0.001). For ESS, JZP-110 was more efficacious relative to placebo after 1 (P <0.0001) and two weeks (P = 0.0002); final ESS scores were 10.8 with JZP-110 and 15.2 with placebo, changes of -6.7 and -2.4, respectively. JZP-110 was generally well tolerated; the most common adverse events with JZP-110 were nausea (12%), noncardiac chest discomfort (9.1%), and headache (9.1%). CONCLUSIONS: The efficacy of JZP-110 for impaired wakefulness and excessive sleepiness was observed at 150-300 mg/day and as early as one week after initiating treatment (Clinicaltrials.gov identifier NCT01485770).

Sleep apnea and sports performance.

Obstructive sleep apnea is a significant medical disorder that is increasingly recognized for its wide-ranging effects on physical and mental health. It can have a profound negative impact on sleep quality, daytime alertness, mood, and cardiovascular health, and effects on metabolic and endocrinologic parameters. There is little known about the prevalence and presentation of apnea in athletes and its potential effect on athletic performance. A high index of suspicion for apnea should exist, particularly in those who have anatomic features and symptoms consistent with the disorder. This article reviews pathophysiology, diagnostic modalities, and treatment interventions.