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Study Objectives Post hoc analyses from the phase 3 REST-ON trial evaluated efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) vs placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2). Methods Participants were stratified by narcolepsy type and randomized 1:1 to ON-SXB (4.5 g, week 1; 6 g, weeks 2–3; 7.5 g, weeks 4–8; and 9 g, weeks 9–13) or placebo. Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups. Results The modified intent-to-treat population comprised 190 participants (NT1, n=145; NT2, n=45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, P Conclusions Clinically meaningful improvements of a single ON-SXB bedtime dose were shown for daytime sleepiness and DNS in NT1 and NT2, with less power for the limited NT2 subgroup.

Introduction Narcolepsy, particularly type 1 (NT1), is often comorbid with obesity. FT218 (LUMRYZ™) is an investigational once-nightly sodium oxybate (ON-SXB) formulation whose efficacy and safety were shown in the phase 3 REST-ON clinical trial (NCT02720744). Methods REST-ON was a 13-week, randomized (1:1), double-blind, placebo-controlled multicenter study in patients ≥16 years old with NT1/NT2. Stable concomitant stimulant use was permitted. A post hoc analysis of participants in the ON-SXB group experiencing ≥5% weight loss (weight-loss group) was conducted. Results In REST-ON (n=212), mean participant age was 31.2 years (range, 16–72), 67.9% were female, 75.5% were white, 76.4% had NT1, mean baseline BMI was 28.1 kg/m2 (range, 16.9–71.9), and 61.3% were taking stimulants. At week 13, 17.8% (19/107) of participants receiving ON-SXB experienced ≥5% weight loss vs 3.8% (4/105) of participants receiving placebo (P< 0.001). Compared to the REST-ON population, the weight-loss group had similar age and proportion of NT1 diagnosis, a smaller proportion was female, and a higher proportion was white and was taking stimulants. At baseline, mean BMI was 25.6 kg/m2 (range, 20.3–34.0) in the weight-loss group, 47.4% (9/19) were overweight (BMI 25.0–29.9 kg/m2) or obese (BMI >30 kg/m2); none were underweight (BMI < 18.5 kg/m2). At week 13, 31.6% (6/19) remained overweight or obese; none were underweight. Excessive daytime sleepiness was significantly improved from baseline to week 13 (ON-SXB 9 g) in the weight-loss group vs the ON-SXB group without weight loss (Maintenance of Wakefulness test, P< 0.05; Epworth Sleepiness Scale score, P< 0.001). Adverse events of nausea and vomiting were more frequent in the weight-loss group vs the ON-SXB group without weight loss; however, rate of discontinuations owing to AEs in the weight-loss group was approximately half that of the ON-SXB group without weight loss. Conclusion These data expand the body of knowledge regarding weight loss during treatment with sodium oxybate. Given the high proportion of comorbid obesity among people with narcolepsy, the additional benefit of potential weight loss with sodium oxybate may further inform treatment selection. Whereas ON-SXB was effective overall, further exploration of possible increased pharmacologic response in certain subgroups should be evaluated. Support (if any) Avadel Pharmaceuticals

Introduction The pivotal phase 3 REST-ON trial (NCT02720744) evaluated the efficacy and safety of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation for treatment of adults with narcolepsy. In REST-ON, ON-SXB met its 3 coprimary endpoints: improvement in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating (% much/very much improved), and number of weekly cataplexy attacks at all doses tested (P< 0.001 vs placebo). The safety profile of ON-SXB was consistent with that of immediate-release (IR) SXB. The ongoing RESTORE trial (NCT04451668) is an open-label/switch study evaluating the safety and tolerability of ON-SXB. Methods Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive are eligible for RESTORE. Initial doses were 4.5 g/night or equivalent/closest to the previous total IR oxybate dose/night for those switching; incremental adjustments (1.5 g/week; maximum dose, 9 g/night) were allowed. Safety data for participants receiving ≥1 dose of ON-SXB as of 01 July 2022 are reported here. Results This analysis includes interim data from 180 participants (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]); mean age is 35 years [range, 16–84]). Most participants who reported an adverse event (AE; n=105 [58.3%]) had AEs that were mild (61.9%) or moderate (32.3%) in severity. Three participants had serious AEs (abscess, deep vein thrombosis, rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and all 3 participants continued in the study. Adverse drug reactions (ADRs; ie, AEs related/possibly related to study drug) were reported by 76 (42.2%) participants with 6 (3.3%) participants discontinuing ON-SXB owing to ADRs. ADRs occurring in ≥3% of participants were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%). Conclusion Interim data from the RESTORE study indicate that ON-SXB is generally well tolerated with a low rate of discontinuation owing to ADRs. If granted final FDA approval, ON-SXB will offer adults with narcolepsy a once-at-bedtime oxybate treatment option. Support (if any) Avadel Pharmaceuticals

Introduction Sodium oxybate (SXB) is a standard-of-care treatment for adults with narcolepsy. Existing oxybate formulations are immediate release (IR), requiring patients to awaken for a second dose 2.5–4 hours after the first bedtime dose. Once-nightly SXB (ON-SXB; FT218), an investigational extended-release formulation, replaces this middle-of-the-night dosing with a once-at-bedtime regimen. RESTORE (NCT04451668) is an open-label/switch study evaluating the safety/tolerability of ON-SXB and patient preferences for ON-SXB or IR oxybate. Methods RESTORE includes participants aged ≥16 years with narcolepsy type 1 or 2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive. Initial doses for participants switching from IR oxybate are equivalent/closest to the previous total dose/night; incremental adjustments (1.5 g/week; maximum, 9 g/night) are allowed. A nocturnal adverse event (AE) questionnaire about switch participants’ IR oxybate experience in the previous 3 months was completed at baseline. Switch participants completed the preference questionnaire after 3 months of ON-SXB treatment. Results Data available from preference questionnaires (n=78) and nocturnal AE questionnaires (n=130) were analyzed at the interim data cutoff (01 July 2022). Most common AEs thus far were nausea, headache, and somnolence. The once-nightly dosing regimen was preferred by 93.6% (73/78) of participants. The second nightly IR oxybate dose was unintentionally missed in the previous 3 months by 65.4% (85/130) of switch participants; 80.2% (73/91) who intentionally and/or unintentionally missed the second dose felt worse the next day. Participants who took their second nightly IR oxybate dose >4 h after the first dose (51/130 [39.2%]) reported being somewhat, quite a bit, or extremely groggy/unsteady the next morning (26/51 [51.0%]). Inconvenience of the second dose was reported by 70.8%. Other issues related to the second dose were anxiety (29.2%) and the need to be woken by someone else (23.1%). In the past 3 months, 118 participants (90.8%) arose from bed after waking to take the second dose; 9 of these participants reported having fallen, with 5 reporting injuries. Conclusion These interim RESTORE data demonstrate patient preference for once-at-bedtime dosing of ON-SXB and indicate treatment burden associated with twice-nightly IR oxybate. Support (if any) Avadel Pharmaceuticals

Introduction Tonic motor activation (TOMAC) is a noninvasive medical device therapy that has been shown to reduce symptoms of refractory restless legs syndrome (RLS). Here, we evaluated the effects of TOMAC on subjective sleep quality. Methods One hundred and thirty-three adults with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for 4 weeks. Participants were instructed to self-administer a 30-minute TOMAC session bilaterally over the head of the fibula to electrically stimulate the peroneal nerve whenever RLS symptoms presented. Sleep quality was assessed through prespecified analysis of changes to Medical Outcomes Study Sleep Scale (MOS-Sleep) Sleep Problems Index I (MOS-I) and II (MOS-II) scores from baseline to Week 4. Post hoc t-tests were conducted on each MOS-Sleep item included in the MOS-I or MOS-II. Results MOS-I score changed by -11.8 points (48.5 to 36.7) for TOMAC and -2.8 points for sham (44.5 to 41.7), a difference of -9.0 points (p< 0.001). MOS-II score changed by -13.7 points (52.5 to 38.9) for TOMAC and -4.0 points for sham (48.3 to 44.3), a difference of -9.7 points (p< 0.001), which exceeds the proposed minimal clinically important difference (MCID) of 6 points. Post hoc analysis demonstrated statistically significant reductions in trouble falling asleep (item #7; -34.0% for TOMAC vs. -5.8% for sham; p< 0.01) and trouble staying awake during the day (item #9; -33.6% for TOMAC vs. -2.1% for sham; p< 0.05), which exceeded the standard MCID threshold of 30% relative to baseline. Conclusion For adults with refractory RLS, TOMAC improved subjective sleep quality, sleep latency, and daytime somnolence relative to sham control. Each of these improvements represented clinically important improvements. These data demonstrate that TOMAC can provide meaningful improvements to sleep quality and daytime functioning for patients with refractory RLS. Support (if any) Funding was provided by Noctrix Health, Inc.

The study aims to explore the level and relationship between intrapersonal intelligence and the decision-making ability of higher secondary school students. The study employed a survey-based quantitative method. The sample includes 500 higher secondary level school students in West Bengal, India. The investigators applied two self-made questionnaires, one for measuring intrapersonal intelligence and another for measuring decision-making ability. The results reveal that gender (3.22, p

Introduction: Anemia is a substantial public health problem that happens worldwide with higher prevalence noted in children less than 5 years and rural children. The studywas aimed to explore the keypredictors of anemia of study population in rural setting of Bangladesh. Methodology & Materials: This cross-sectional study was conducted in the rural Bangladesh from 1 July 2018 to December 2019. Under-five children aged six months to below sixty months were enrolled in the study. Data were collected through face-to-face interview from attending primary caregiver and from the results of laboratory tests of blood sample from target children. Data were analyzed through SPSS 23 software. Initially univariate analysis was done to identify predictors of anaemia followed by multivariate analysis to explore the key predictors through logistic regression. Results: A total data of258 under-five children aged 6-59 month were included in this study from the rural areas of Bangladesh. Among the studied children overall prevalence of anaemia was found 61.8%. The significant predictors (p

What is this summary about? This is a plain language summary of an article originally published in the journal Sleep. Once-nightly sodium oxybate (ON-SXB for short; also known as FT218) is a potential treatment for excessive daytime sleepiness (EDS for short) and sudden muscle weakness known as cataplexy. The US Food and Drug Administration (FDA) is deciding whether to approve ON-SXB to be prescribed to adults with narcolepsy. The REST-ON clinical study looked at whether ON-SXB was better than a substitute that had no medicine in it (called a placebo) at treating narcolepsy symptoms. What were the results? The results of this study showed that people who took ON-SXB were able to stay awake longer during the day, felt less sleepy in the daytime, had less cataplexy, and were more improved overall than people who took placebo. Common side effects with ON-SXB were nausea, vomiting, dizziness, bedwetting, and headache. What do the results mean? If approved by the FDA, people with narcolepsy may have the option to choose a form of sodium oxybate that they only have to take once at bedtime. They could avoid taking a second middle-of-the-night dose. ClinicalTrials.gov NCT number: NCT02720744