Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) was a phase 4, prospective, multicenter, single-arm, open-label, multiple-cohort study of individuals with idiopathic hypersomnia or narcolepsy evaluating safety and effectiveness of low-sodium oxybate (LXB; Xywav®) treatment on sleep and daytime symptoms. Results from the idiopathic hypersomnia cohort are reported here. The DUET study included a screening period (with a 2-week washout for current oxybate users), an 8-day baseline (BL) period, a 2- to 8-week LXB titration period, a 2-week stable-dose period, an 8-day end-of-treatment period (EOT) period, and a 2-week safety follow-up. The primary endpoint was the change in Epworth Sleepiness Scale (ESS) score from BL to EOT. Secondary endpoints for the idiopathic hypersomnia cohort included change in Idiopathic Hypersomnia Severity Scale (IHSS) total score; Patient Global Impression of Change (PGI-C) and Severity (PGI-S) for overall idiopathic hypersomnia disease, sleep inertia, and fatigue; and changes in sleep quality and feeling rested upon awakening (from self-reported daily sleep diary). Exploratory outcomes included sleep patterns measured by actigraphy, the British Columbia Cognitive Complaints Inventory, Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem. Incidence and severity of treatment-emergent adverse events (TEAEs) were assessed. Forty-six participants with idiopathic hypersomnia enrolled and took LXB for ≥ 1 night after the BL period; n = 40 completed. Most enrolled participants were female (80.4 Calcium, magnesium, potassium, and sodium oxybates (also called low-sodium oxybate [LXB; Xywav®]) is approved for treating adults with idiopathic hypersomnia. Low-sodium oxybate is also approved for treating excessive daytime sleepiness or cataplexy in people aged ≥ 7 years with narcolepsy. The DUET study tested sleep and daytime symptoms and daily activities in people with idiopathic hypersomnia who took LXB. Before starting LXB, people completed tests to measure their symptoms. They then started taking LXB. The study doctors adjusted the LXB dosage over 2–8 weeks to find the best dosage for each person. Once found, patients remained on this dosage for 2 more weeks. At the end of the study, tests were repeated to see how the best dosage of LXB affected their sleep and daytime symptoms, daily tasks, and work. Forty-six people with idiopathic hypersomnia started taking LXB, and 40 people completed the study. After LXB treatment, patients had less severe idiopathic hypersomnia symptoms. They felt less sleepy during the day and had less fatigue. They felt that their sleepiness after waking (sleep inertia) was improved. People spent less time sleeping at night and had fewer awakenings. They also said they had better sleep and felt more rested after waking up. Daily tasks and work productivity also improved. The most common side effects with LXB were nausea, dizziness, headache, and vomiting, which happened in more than 10

A phase 4, prospective, open-label study of low-sodium oxybate (LXB) in narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia included novel symptom outcomes important to patients (Jazz DUET; NCT05875974; registered 16 May 2023). Primary results from the narcolepsy cohort, including LXB effectiveness (nighttime sleep/daytime symptoms/overall disease severity) and safety are reported here. DUET included screening, 8-day baseline (BL; off-LXB), 2–8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT; on-LXB), and safety follow-up periods. At BL and EOT, participants underwent nocturnal polysomnography (PSG) and completed Epworth Sleepiness Scale (ESS; primary endpoint), Narcolepsy Severity Scale (NSS [NT1]; NSS-2 [NT2]), and Patient Global Impression of Severity (PGI-S) and Change (PGI-C); eDiaries for sleep quality and cataplexy (NT1 only) were completed daily for 8 days before PSGs. Least-squares mean (LSM) changes were adjusted for BL values. Thirty-four participants completed the study and were analyzed (NT1, n = 16; NT2, n = 18); LSM (SE) change in ESS score (BL to EOT), − 7.7 (0.9), P < 0.0001. At EOT versus BL, transitions to lighter stages of sleep decreased (LSM [SE] − 13.1 [2.9], P < 0.0001), N3 duration increased (45.0 [8.8] min, P < 0.0001), and nocturnal awakenings decreased (− 3.2 [0.9], P = 0.0013). LSM [SE] changes in NSS and NSS-2 scores were − 19.7 (2.7) and − 11.3 (1.6). Most participants reported improved sleep quality and overall narcolepsy disease and fewer cataplexy attacks. Treatment-emergent adverse events were consistent with the known LXB safety profile. DUET study results demonstrated novel nighttime sleep/daytime symptom improvements in participants with narcolepsy treated with open-label LXB. ClinicalTrials.gov identifier, NCT05875974. Low-sodium oxybate (LXB; Xywav®), a medication that contains calcium, magnesium, potassium, and sodium oxybates, is approved for treating excessive daytime sleepiness or cataplexy (sudden muscle weakness) in people aged 7 years and older with narcolepsy. LXB is also approved for treating idiopathic hypersomnia in adults. The DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) study tested sleep and daytime symptoms in people with narcolepsy who took LXB. Before starting LXB, people in the study completed tests to measure their symptoms and sleep patterns. Then they started taking LXB. Study doctors adjusted LXB doses over 2–8 weeks to find the best dosage for each person. After the best dosage was found, people took that dosage for 2 more weeks. At the end of the study, people took the tests again while taking LXB. The study looked at changes in test findings before and after taking the best dosage of LXB. People took LXB for 5–12 weeks. Fifty-five people with narcolepsy started taking LXB. After LXB treatment, people had less daytime sleepiness. They had fewer sleep disruptions, like transitions from deeper to lighter stages. They got about 45 min more of deep sleep at night. They also woke up less frequently at night. After LXB treatment, most people said their overall narcolepsy disease was better. The most common side effects were nausea, dizziness, headache, drowsiness, and vomiting. People with narcolepsy who took LXB had less daytime sleepiness and less disrupted nighttime sleep than before taking LXB.

Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on outcomes including polysomnography (PSG)-based sleep architecture in participants with idiopathic hypersomnia or narcolepsy (type 1 [NT1] or 2 [NT2]). DUET included a screening period (2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period (SDP), 8-day end-of-treatment period (EOT), and 2-week safety follow-up. Participants underwent nocturnal PSG (ad libitum protocol) at BL and EOT. PSGs were scheduled to allow a minimum of 10 hours in bed, unless the participant naturally awakened earlier; bedtime was determined by habitual bedtime. PSG recordings were centrally scored. Data were analyzed for participants in the narcolepsy cohort completer set. Total shifts from deeper to lighter sleep stages was defined as N1/N2/N3/REM to wake and N2/N3/REM to N1. Key secondary endpoints (total stage shifts, N3 duration) were controlled for multiplicity with sequential testing; other P-values are considered nominal. Fifty-five participants with narcolepsy enrolled (NT1, n=26; NT2, n=29); 34 completed the study (NT1, n=16; NT2, n=18). Most were female (73%) and White (80%) (mean±SD age, 33.4±12.9 years). Mean±SD total sleep time (TST) at BL/EOT was 453.2±80.1/452.4±70.0 minutes (LSM change [95% CI]: –0.78 [–23.7, 22.1]; P=.9451). Mean±SD number of total shifts from deeper to lighter sleep stages at BL/EOT was 54.6±28.0/41.6±25.6 (LSM [95% CI]: –13.1 [–19.0, –7.1]; P<.0001 [controlled for multiplicity]). Mean±SD time spent in N1 at BL/EOT was 45.3±28.4/37.2±25.2 minutes (LSM [95% CI]: –8.1 [–14.9, –1.4]; P=.0196), % of stage was 10.4%/8.2% (P=.0037); in N2 was 241.8±61.2/243.3±76.1 minutes (LSM [95% CI]: 1.5 [–23.6, 26.6]; P=.9040), 53.1%/53.2% (P=.9869); in N3 was 61.1±34.8/106.1±69.5 minutes (LSM [95% CI]: 45.0 [27.0, 63.0]; P<.0001 [controlled for multiplicity]), 13.7%/24.0% (P<.0001); and in REM was 105.0±42.7/65.8±33.1 minutes (LSM [95% CI]: –39.2 [–50.8, –27.5]; P<.0001), 22.8%/14.7% (P<.0001). Participants with narcolepsy taking open-label LXB showed negligible change in TST and N2, increased N3, decreased N1 and REM, and fewer shifts from deeper to lighter stages of sleep. Jazz Pharmaceuticals

Objective/Background Central disorders of hypersomnolence (CDH), including narcolepsy, idiopathic hypersomnia, and recurrent hypersomnia, are rare conditions that pose challenges in sleep medicine fellowship training. Limited exposure to these disorders, variability in training experiences, and growing complexity of diagnostic tools and treatment options contribute to gaps in education. This study aimed to assess perceptions of training adequacy in CDH among sleep medicine program directors and recent fellowship graduates. Patients/Methods A cross-sectional survey was conducted between April 2024 and July 2024 among US board-certified sleep physicians, including program directors contacted through a sleep medicine fellowship program listserv, and their recent fellowship graduates. Surveys assessed perceptions of training in diagnosing and managing CDH, including exposure to diagnostic tools, patient populations, and pharmacological treatments. Responses were summarized using descriptive statistics. Results Of 110 program directors contacted, 29 (26.4%) responded, and 48 (6.5%) of 740 eligible graduates participated. Program directors and graduates reported adequate exposure to narcolepsy and idiopathic hypersomnia; exposure to recurrent hypersomnia was lower. Both groups reported confidence in adequacy of training in most diagnostic methods (polysomnography, multiple sleep latency test, and Epworth Sleepiness Scale); confidence with actigraphy was lower. Gaps were identified in training for longitudinal care during medical management of CDH, and exposure to certain medications (eg, lithium) was limited. Conclusions Survey findings demonstrate adequacy of training in diagnosing CDH but suggest some gaps in training regarding rare conditions and advanced treatment and management, highlighting needs for targeted educational resources and standardized curricula. Clinical trial registration Not applicable.

To assess the prevalence of hypertension, risk of developing hypertension, and risk of mortality among individuals with narcolepsy or idiopathic hypersomnia in Denmark, we performed a retrospective, nationwide, cohort analysis of the Danish National Patient Registry (DNPR). Adults (aged ≥ 18 years) diagnosed with narcolepsy or idiopathic hypersomnia between 1 January 1998 and 31 December 2020 were matched 1:4 with non-narcolepsy/non-idiopathic hypersomnia controls based on key demographics (age, sex, marital status, geographic location). Outcomes included hypertension prevalence at diagnosis, incident hypertension after diagnosis, and mortality risk. For individuals with narcolepsy (n = 1760) versus matched controls (n = 7012), the odds ratio (OR) for having prevalent hypertension at diagnosis was 1.50 (95% confidence interval [CI], 1.28-1.76); individuals with narcolepsy also had higher risk (hazard ratio [HR; 95% CI]) of developing hypertension after diagnosis (1.40 [1.23-1.60]) and of mortality (1.25 [1.08-1.44]). Individuals with idiopathic hypersomnia (n = 3067) versus matched controls (n = 12,241) had higher odds (OR [95% CI]) of having prevalent hypertension at diagnosis (1.84 [1.64-2.05]) and higher risk (HR [95% CI]) of developing hypertension after diagnosis (1.38 [1.28-1.50]); mortality risk was similar for idiopathic hypersomnia versus controls (HR [95% CI]: 0.94 [0.84-1.06]). These data provide one of the first DNPR examinations of cardiovascular burden and mortality in individuals with idiopathic hypersomnia, finding greater prevalence and risk of developing hypertension in people with narcolepsy or idiopathic hypersomnia compared with matched controls. Mortality risk was also higher in people with narcolepsy. Findings support that the cardiovascular burden experienced by these populations should be considered during treatment evaluation. Please find the PLS file attached for your reference.

OBJECTIVES:Prolonged nighttime sleep is a prominent symptom in many patients with idiopathic hypersomnia. The only US Food and Drug Administration-approved treatment for idiopathic hypersomnia is low-sodium oxybate (LXB; Xywav®), for which efficacy and safety were established in a double-blind, placebo-controlled, randomized-withdrawal study (NCT03533114). This post hoc analysis evaluated the effect of LXB treatment on sleep time. METHODS:Eligible participants (aged 18-75 years, primary diagnosis of idiopathic hypersomnia) began LXB treatment in an open-label titration and optimization period (10-14 weeks), entered a stable-dose period (SDP; 2 weeks), and were randomized to continue LXB or placebo in a double-blind, randomized-withdrawal period (DBRWP; 2 weeks). Sleep parameters, including 24-hour self-reported total sleep time (TST), nocturnal TST, and total nap duration, were analyzed using daily electronic sleep diary data collected ≥2 weeks during 3 different study periods. RESULTS:In total, 3917 daily records from 148 participants were analyzed. During open-label LXB treatment, from baseline to the end of SDP, there were decreases in median 24-hour TST (from 513.3 minutes to 468.8 minutes), nocturnal TST (from 495.0 minutes to 454.3 minutes), and total nap duration (from 16.3 minutes to 7.8 minutes). During DBRWP, estimated median differences between LXB and placebo in 24-hour TST, nocturnal TST, and total nap duration were -25, -9, and -12 minutes, respectively. Common treatment-emergent adverse events (≥10 % of participants) were nausea, headache, dizziness, anxiety, and vomiting. CONCLUSIONS:Open-label LXB treatment in adults with idiopathic hypersomnia was associated with reductions in 24-hour TST, nocturnal TST, and total nap duration.

OBJECTIVE/BACKGROUND:To assess the clinical and socioeconomic burden of narcolepsy and idiopathic hypersomnia (IH) in Denmark. PATIENTS/METHODS:This retrospective cohort study using Danish National Patient Registry data included individuals diagnosed with narcolepsy or IH (1/1/2005-12/31/2017). Individuals with narcolepsy were matched 1:4 with controls without narcolepsy; matching was repeated for individuals with IH. Comorbidities, employment, income, and healthcare costs were assessed in the 3 years before and after diagnosis using logistic regression and generalized linear models. RESULTS:1183 individuals with narcolepsy (4728 controls) and 1801 individuals with IH (7204 controls) were assessed. Before diagnosis, individuals with narcolepsy had higher odds (odds ratio [OR]; 95 % confidence interval [CI]) of having nervous system (7.92 [6.46, 9.71]) or circulatory system diseases (2.45 [1.95, 3.07]) than controls, in addition to higher unemployment (2.30 [1.79, 2.96]). Individuals with narcolepsy had lower mean income before (€22,076 vs €26,538) and after (€21,786 vs €27,090) diagnosis and higher mean healthcare costs before (€4547 vs €1909) and after (€7411 vs €2178) diagnosis. Before diagnosis, individuals with IH had higher odds (OR [95 % CI]) of having nervous system (9.37 [7.93, 11.08]) or circulatory system diseases (1.80 [1.49, 2.16]) than controls, in addition to higher unemployment (1.73 [1.42, 2.10]). Individuals with IH had lower mean income before (€31,947 vs €34,503) and after (€30,262 vs €35,139) diagnosis and higher mean healthcare costs before (€4050 vs €1840) and after (€5124 vs €2106) diagnosis. CONCLUSIONS:Danish individuals with narcolepsy or IH had a greater clinical and socioeconomic burden than controls.

BackgroundThe impact of incremental peritoneal dialysis (PD) on outcomes is poorly understood, and there is a paucity of evidence informing best practices regarding the dialysis dose at the commencement of PD. This international prospective cohort study aimed to compare PD prescription practices at dialysis commencement and their subsequent association with clinical outcomes.MethodsAdult patients who started PD for less than three months at the time of enrolment in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) between 1 January 2014 and 31 December 2017 were included. Patients were defined as initiating incremental PD if prescribed a total of <4 exchanges/day for continuous ambulatory peritoneal dialysis (CAPD) or, with dry days or having PD less than seven days per week for automated peritoneal dialysis (APD). All other prescriptions were considered standard PD. The primary outcome was the transfer to haemodialysis (HD). Secondary outcomes included peritonitis rate, time to first peritonitis and mortality. Logistic regression analysed PD uptake and the Cox proportional hazards regression model analysed HD transfer, peritonitis and patient survival.ResultsOverall, 1365 PD patients from 128 facilities across seven countries were included. Fewer individuals started on incremental PD than standard PD (37% vs 63%, p < 0.001). Higher incremental PD uptake was associated with receiving treatment in Japan (odds ratio [OR] 2.35, 95% CI 1.05-5.26, p = 0.04; ref: Canada), age >75 years (OR 1.51, 95% CI 1.02-2.24, p = 0.04), icodextrin use (OR 8.54, 95% CI 6.26-11.64, p < 0.001), lower serum creatinine concentration at PD start (OR 1.01, 95% CI 1.01-1.01, p = 0.007) and higher number of PD patients at a facility (OR 1.01, 95% CI 1.00-1.01, p = 0.02). Crude HD transfer rates for the incremental and standard PD groups were 0.14 (95% CI, 0.12-0.16) and 0.15 (95% CI, 0.13-0.17) per patient-year of follow-up, respectively (incidence rate ratio [IRR], 0.93; 95% CI, 0.75-1.15; p = 0.49). There was no significant difference in the hazard of HD transfer between the incremental and standard PD groups (hazard ratio [HR] 0.87, 95% CI 0.68-1.12, p = 0.29). There were also no differences between the two groups concerning peritonitis and mortality.ConclusionsIncremental PD start was prescribed in approximately one-third of patients and, in low certainty evidence, was associated with comparable risks of HD transfer, peritonitis and death.

Measurement tools for sleep inertia, a common and important idiopathic hypersomnia symptom, are limited. For individuals with idiopathic hypersomnia, this post hoc analysis proposes a minimal clinically important difference (MCID) for the Sleep Inertia Visual Analog Scale (SI-VAS), which assesses difficulty waking up. Data from the pivotal phase 3, double-blind, placebo-controlled, randomized withdrawal study (NCT03533114) of low-sodium oxybate in adults with idiopathic hypersomnia were used to estimate an SI-VAS MCID anchored to the Patient Global Impression of Change, Idiopathic Hypersomnia Severity Scale, and Functional Outcomes of Sleep Questionnaire. Of 109 participants included, the majority female (69.7 Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension; URL: https://www.clinicaltrials.gov/study/NCT03533114 ; Identifier: NCT03533114. Bogan RK, Fuller DS, Whalen M, Casstevens C, Schneider LD. A minimal clinically important difference for the sleep inertia visual analog scale in idiopathic hypersomnia. J Clin Sleep Med. 2025;21(7):1209–1216.

BACKGROUND:People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS:We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS:Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, -4.1 [95% CI, -6.9 to -1.4] mm Hg; 1-sided P=0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS:People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05869773.

OBJECTIVE/BACKGROUND:Limited research assesses cardiovascular risk in people with idiopathic hypersomnia. This study compared cardiovascular conditions or events among individuals with idiopathic hypersomnia with those among matched non-idiopathic hypersomnia controls. PATIENTS/METHODS:Claims from Merative™ MarketScan® Research Databases (12/2013-2/2020) were analyzed. Eligible individuals with idiopathic hypersomnia were ≥18 years of age upon cohort entry, continuously enrolled for 365 days before and after cohort entry (gaps ≤30 days allowed), and without cataplexy. Individuals with idiopathic hypersomnia entered the cohort upon their earliest medical claim with an idiopathic hypersomnia diagnosis code. Controls were matched 5:1, without replacement, to individuals with idiopathic hypersomnia using demographic characteristics. Odds of prevalent cardiovascular conditions or events during the 2-year assessment period (365 days before and after cohort entry date) were compared using unconditional logistic regression. Results were reported as odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS:Final cohorts included 11,412 individuals with idiopathic hypersomnia and 57,058 matched controls. Odds (OR, 95 % CI) of cardiovascular disease (2.26, 2.14-2.38), major adverse cardiovascular event (2.08, 1.89-2.30), stroke (2.07, 1.87-2.29), hypertension diagnosis or antihypertensive use (2.02, 1.93-2.12), heart failure (1.97, 1.76-2.20), atrial fibrillation (1.91, 1.66-2.20), myocardial infarction (1.74, 1.42-2.12), and coronary revascularization (1.58, 1.12-2.17) were higher in individuals with idiopathic hypersomnia than matched controls. CONCLUSIONS:Individuals with idiopathic hypersomnia had higher odds of prevalent cardiovascular conditions or events than matched controls. These results reinforce that clinicians should be aware of patients' cardiovascular risk profiles when selecting idiopathic hypersomnia treatments.

Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) assessing the effectiveness of low-sodium oxybate (LXB; Xywav®) treatment on daytime and nighttime symptoms in participants with narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia. Data presented are from the narcolepsy cohort. DUET included a screening period (with 2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period, 8-day end-of treatment (EOT) period, and 2-week safety follow-up. The primary endpoint was change in Epworth Sleepiness Scale (ESS) score from BL to EOT. Key secondary endpoints for the narcolepsy cohort included change in polysomnography parameters: total shifts from deeper to lighter sleep stages, stage N3 sleep duration (minutes), and number of awakenings. Additional endpoints included Patient Global Impression of Change (PGIc)–overall narcolepsy disease. Primary and key secondary endpoints were controlled for multiplicity with sequential testing; other P-values are considered nominal. Fifty-five narcolepsy participants enrolled and were dosed with LXB (NT1, n=26; NT2, n=29); 13 transferred to another cohort and 34 were completers (NT1, n=16; NT2, n=18). Enrolled participants were mostly female (72.7%) and White (80.0%); mean (SD) age was 33.4 (12.9) years (NT1=34.6 [12.6]; NT2=32.4 [13.2]). For completers, least-squares mean (LSM) (SE) changes in ESS score were −7.7 (0.9), P<.0001, overall; NT1=−6.5 (1.4), P<.0001; NT2=−8.8 (1.3), P<.0001. Compared with BL, sleep architecture at EOT showed fewer deeper to lighter sleep stage shifts (LSM [SE]: −13.1 [2.9], P<.0001, overall; NT1=−13.9 [4.3], P=0.0029; NT2=−12.3 [4.1], P=0.0050); increased stage N3 sleep (minutes) (45.0 [8.8], P<.0001, overall; NT1=49.8 [13.0], P=0.0006; NT2=40.8 [12.3], P=0.0023); and fewer awakenings (−3.2 [0.9], P=0.0015, overall; NT1=−4.1 [1.4], P=0.0056; NT2=−2.3 [1.3], P=0.0771). Most participants (93.3%, n=30; NT1, 86.7%, n=15; NT2, 100%, n=15) reported improvement (very much, much, minimally) in overall narcolepsy disease on PGIc. Treatment-emergent adverse events were consistent with the known safety profile of LXB. Participants with NT1 and NT2 taking open-label LXB showed improvements in daytime sleepiness (decreased ESS scores) and reduced symptom burden (improved PGIc), which paralleled improvements in sleep architecture and disruption. Jazz Pharmaceuticals

OBJECTIVE:Low-sodium oxybate (LXB) is approved in the United States for treating cataplexy or excessive daytime sleepiness in patients aged ≥7 years with narcolepsy and idiopathic hypersomnia in adults. This post hoc analysis evaluated LXB effects on weight in patients with narcolepsy or idiopathic hypersomnia from two phase 3 studies. METHODS:Adults with narcolepsy with cataplexy or idiopathic hypersomnia began LXB treatment during open-label titration (10-14 weeks), followed by 2-week stable-dose periods (SDP). RESULTS:Safety populations comprised 201 participants with narcolepsy (75 previously taking sodium oxybate) and 148 with idiopathic hypersomnia (oxybate-naive at study entry); most were overweight or obese at baseline (narcolepsy, 67 %; idiopathic hypersomnia, 60 %). Least-squares (LS) mean (95 % CI) weight changes at end of SDP were -1.0 (-2.2, 0.1), -3.5 (-4.7, -2.3), and -2.3 (-3.4, -1.1) kg in oxybate-naive participants with narcolepsy and normal weight, overweight, and obese, respectively, and 0.0 (-1.6, 1.6), -0.7 (-2.2, 0.8), and 0.3 (-1.1, 1.7) kg in participants with narcolepsy previously taking oxybate and normal weight, overweight, and obese, respectively. In oxybate-naive participants with idiopathic hypersomnia, LS mean (95 % CI) changes at end of SDP were -2.2 (-3.5, -0.8), -2.6 (-4.1, -1.2), and -3.4 (-4.9, -1.8) kg in normal weight, overweight, and obese participants, respectively. Weight loss ≥5 % at end of SDP occurred in 26 % of oxybate-naive participants with narcolepsy, 5 % of those with narcolepsy previously taking oxybate, and 30 % with idiopathic hypersomnia. CONCLUSION:Open-label LXB was associated with modest weight loss in participants with narcolepsy with cataplexy or idiopathic hypersomnia.