Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) is a phase 4, prospective, multicenter, single-arm, open-label interventional study that comprehensively evaluates low-sodium oxybate effects on sleep architecture and daytime/nighttime symptoms in participants with idiopathic hypersomnia or narcolepsy. Multiple assessments, including overnight polysomnography (PSG), are needed to generate robust, relevant data, but these assessments may impose a burden on study participants. A patient advisory board was convened to understand patient perspectives and assess opportunities to incorporate patient feedback into the study protocol. Methods Advisors completed a premeeting survey, then attended a 3-hour advisory board meeting with the study sponsor. Five main topics were discussed: feasibility of oxybate washout for participants entering the study on treatment, burden of assessments, relevance of specific symptom evaluation to participants, value of reporting individualized data back to participants, and burden of overnight visits. Results The advisory board included 2 people with idiopathic hypersomnia and 4 people with narcolepsy. All 6 advisors had experience with patient advocacy, and at least 1 had been a clinical trial participant; these experiences may help give voice to a broader patient community. Premeeting survey responses were reviewed and discussed during the meeting. Based on advisor input, the final study protocol incorporated several points, including support for participants undergoing oxybate washout (eg, transportation, childcare, and meal service, as needed), additional breaks between assessments, moving assessments from evening to morning to reduce participant burden, measuring fatigue separately from sleepiness, and suggestions to make participants more comfortable for overnight visits. Advisors noted the high value of reporting individualized data back to study participants—particularly PSG data, with specific interest in number of awakenings, duration of rapid eye movement sleep, and duration of slow-wave sleep. In addition to these changes, study materials were developed to help participants prepare for overnight visits, and a checklist of items to bring to these visits was created. Conclusion The final DUET study design incorporated patient-centric elements recommended by a patient advisory board. Implementation of these elements is anticipated to reduce participant burden, improve participant experience, enhance recruitment and retention, and facilitate collection of meaningful and comprehensive data. Support (if any) Jazz Pharmaceuticals

To compare comorbid conditions between patients with idiopathic hypersomnia (IH) and matched non-IH controls.

Analyze response to low-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114) in participants with idiopathic hypersomnia.

Low-sodium oxybate (LXB; calcium, magnesium, potassium, and sodium oxybates; Xywav) contains the same active moiety as high-sodium oxybates (SXBs; SXB [Xyrem] and fixed-dose SXB [Lumryz]), with 92 https://classic.clinicaltrials.gov/ct2/show/NCT04794491 ; Identifier: NCT04794491. Macfadden W, Leary EB, Fuller DS, Kirby MT, Roy A. Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study. J Clin Sleep Med. 2024;20(9):1467–1477.

Abstract Introduction Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy, and idiopathic hypersomnia in adults. LXB contains the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) but with 92% less sodium. Previous studies have reported increased cardiovascular (CV) and cardiometabolic (CM) comorbidities in people with narcolepsy. This post-hoc analysis of a phase 3 trial assessed LXB efficacy and safety in participants with narcolepsy with and without CV/CM comorbidities. Methods Participants 18–70 years of age with narcolepsy with cataplexy optimized/titrated their LXB dose (up to 12 weeks) before entering a 2-week stable-dose period (SDP) (NCT03030599). Following SDP, participants withdrew to placebo or continued LXB during a 2-week double-blind randomized-withdrawal period (DBRWP). Epworth Sleepiness Scale (ESS) scores, cataplexy (average N/week), Patient Global Impression of Change (PGIc) scores, and treatment-emergent adverse events (TEAEs) were assessed in participants with and without CV/CM comorbidities, per medical history. Results Of 201 participants, 69 reported CV/CM comorbidities at baseline (most commonly hypertension and obesity). Participants with and without CV/CM comorbidities, respectively, had mean (SD) BMI of 31.6 (6.4) and 27.2 (5.3); mean age was 43.4 (12.0) and 33.9 (11.0) years; 66.7% and 57.6% were female. Participants randomized to placebo in the DBRWP in both subgroups showed worsening (increases) in ESS scores compared with those randomized to LXB (least squares mean differences, LXB vs placebo [95% CI], with CV/CM comorbidities: −2.6 [−4.5, −0.70], P=0.0077; without CV/CM comorbidities: −2.7 [−4.2, −1.2], P=0.0004; subgroup interaction, P=0.95). Participants without CV/CM comorbidities randomized to placebo had increased cataplexy attacks compared with those taking LXB (median, placebo, 3.0; LXB, 0.0; P< 0.0001); those with CV/CM comorbidities had similar efficacy (placebo, 1.9; LXB, 0.0; P=0.0745). PGIc scores showed worsening in participants randomized to placebo vs LXB in both subgroups (P< 0.0001 for both). Serious TEAEs were reported by 3% of participants with CV/CM comorbidities and 2% of those without. Conclusion In this post-hoc analysis, the efficacy and safety of LXB were similar in participants with narcolepsy with and without CV/CM comorbidities. Support (if any) Jazz Pharmaceuticals

Abstract Introduction Low-sodium oxybate (LXB; Xywav®) and high-sodium oxybate (SXB; Xyrem®) are approved to treat cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy; LXB is also approved for idiopathic hypersomnia in adults. Both are available through the same manufacturer’s Risk Evaluation and Mitigation Strategy (REMS) program under the US Food and Drug Administration, where prescribers and patients receive training and educational materials containing important information about the significant risks, safe handling, and storage of LXB and SXB. The Knowledge, Attitude, and Behavior survey was conducted to document and assess their level of awareness regarding important information about LXB and SXB communicated through the REMS. Methods Internet, telephone, and paper surveys were conducted between October 27, 2022 and February 26, 2023. Survey questions and statements tested each group’s understanding of REMS Key Risk messages (risks associated with LXB and SXB, risk of abuse, dosing and safe handling). Surveys considered LXB and SXB jointly. Results Surveys were completed by 3152 patients and 273 prescribers. Most patient respondents correctly identified risks related to taking LXB and SXB at recommended doses (81.5%); most knew there is a risk of abusing LXB and SXB (89.6%) and correctly identified risks of taking too much of either (93.4%). Most prescriber respondents correctly recognized central nervous system depression (91.6%) and respiratory depression (79.5%) as risks associated with LXB and SXB; most were aware of patterns of misuse (99.3%) and drug-seeking behaviors (96.7%). For twice-nightly regimens, nearly all patients and prescribers, respectively, understood the first dose should be taken at bedtime (99.5%, 98.9%), the second dose should be taken 2.5–4 hours following the first dose (99.0%, 98.9%), and patients should remain in bed for both doses (99.4%, 95.9%). Most patients and prescribers responded correctly regarding proper storage (99.8%, 83.8%), reporting loss or theft (89.6%, 87.5%), and the legality of giving or selling LXB and SXB (98.9%, 99.6%). Conclusion Most patients and prescribers surveyed demonstrated understanding of the risks, dosing instructions, and safe handling of LXB and SXB communicated through the REMS to support safe and effective use. Support (if any) Jazz Pharmaceuticals

What is this summary about? This plain language summary describes a clinical study that looked at the effects of a medicine called low-sodium oxybate (or LXB; XYWAV((R)) [calcium, magnesium, potassium, and sodium oxybates]) in adults with narcolepsy. Narcolepsy is a rare brain disorder that can make people feel extremely sleepy during the day or have symptoms like cataplexy, which is sudden and temporary muscle weakness. This study compared changes in symptoms between people who either switched to placebo or continued with LXB after they had been taking LXB for 14 weeks. The placebo looked and tasted like LXB but did not have the active ingredient. This allowed researchers to see if LXB improved symptoms like cataplexy and extreme daytime sleepiness. What were the results? Cataplexy and daytime sleepiness got worse in people who switched to placebo compared with those who kept taking LXB. This means that LXB worked well to treat symptoms of cataplexy and extreme daytime sleepiness. The most common side effects-defined as any unexpected medical events that happened while taking LXB-were headache, nausea, and dizziness. What do the results mean? LXB lowered the symptoms of cataplexy and daytime sleepiness in people with narcolepsy. LXB is approved in the USA to treat cataplexy or extreme daytime sleepiness (in people with narcolepsy who are 7 years of age and older). LXB is approved in Canada to treat cataplexy in adults with narcolepsy.

Abstract Introduction High sodium intake can increase blood pressure (BP) and future cardiovascular risk. Individuals with narcolepsy have an elevated cardiovascular comorbidity burden before considering medication-specific risks. Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration (FDA) to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy and idiopathic hypersomnia in adults. LXB has the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) but contains 92% less sodium. The objective of XYLO is to measure ambulatory and in-clinic systolic BP (SBP) changes after switching to LXB from a high-sodium oxybate in participants with narcolepsy (NCT05869773). Methods This 6-week, open-label, multicenter, switch study is enrolling participants 18–70 years of age with narcolepsy (type 1 or 2) taking 6–9 g/night of high-sodium oxybate for ≥6 weeks. Hybrid enrollment supports both on-site and decentralized (monitored at the participant’s home by mobile health professionals) participation, and may broaden the pool of eligible participants. After ≥2 weeks on stable high-sodium oxybate dose/regimens (screening period), participants switch to the same dose/regimen of LXB for 6 weeks (intervention period). The primary endpoint is the change in 24-hour SBP from baseline (the most recent screening measurement prior to switching) to the end-of-treatment visit (approximately 6 weeks after switching) measured via 24-hour ambulatory BP monitoring (ABPM). Secondary endpoints evaluate change from baseline to end-of-treatment visit in-clinic SBP, as well as daytime average SBP and nighttime average SBP measured via 24-hour ABPM. Results Recruitment began in June 2023. This study uses a group sequential design with an adaptive sample size target of 57–77 participants completing the 6-week intervention period. This design provides 90% power to detect a mean difference of 3.5 mmHg (a clinically relevant change) in 24-hour SBP (assuming a standard deviation of the differences in 24-hour SBP of 8 mmHg). Conclusion XYLO will enable the assessment of 24-hour BP changes following transition from a high-sodium oxybate to LXB. Planned hybrid enrollment with a decentralized option may increase study access leading to a more diverse clinical trial population. Support (if any) Jazz Pharmaceuticals

Abstract Introduction Although the efficacy and safety of low-sodium oxybate (LXB, Xywav®) in the treatment of idiopathic hypersomnia and narcolepsy are well established, opportunities remain to better understand its impact on sleep architecture and other daytime/nighttime outcomes important to patients and clinicians. Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) is a phase 4, prospective, multicenter, single-arm, open-label interventional study designed with novel methodology and expert input to evaluate the impact of LXB on excessive daytime sleepiness, polysomnographic (PSG) sleep parameters, and functional outcomes in adults with idiopathic hypersomnia or narcolepsy (type 1 or 2). Methods DUET includes a screening period (with a 2-week washout for participants taking oxybate at study entry), 1-week baseline period (off-treatment), 2- to 8-week titration period (for flexible LXB dosing adjustments based on participants’ needs), 2-week stable-dose period, 1- to 2-week end-of-treatment period (on LXB), and safety follow-up (after 2 weeks). To more comprehensively understand the impact of LXB on sleep architecture and other daytime/nighttime outcomes, novel design elements were integrated into the study. Input from an expert advisory board helped refine the study design and ensure that the most relevant elements for patients and clinicians were incorporated into the final DUET protocol. Responses from a premeeting survey of advisors focused on eligibility criteria, suitability of endpoints, newly created questionnaires, and analyses and were discussed during a 4-hour workshop with the study sponsor. Results Advisors were 6 clinicians with expertise in treating patients with idiopathic hypersomnia and narcolepsy and/or with expertise in PSG. Novel design aspects discussed and incorporated into the protocol included PSG conducted with ad libitum sleep duration, objective evaluation of sleep inertia using the Psychomotor Vigilance Test, a new questionnaire for capturing clinician-reported dosing to better understand dosing rationale, evaluation of motor activity during sleep (with PSG), and evaluation of dysautonomia using the Orthostatic Hypotension Questionnaire. Conclusion DUET is the first prospective evaluation of the impact of LXB on sleep architecture (PSG) in patients with idiopathic hypersomnia or narcolepsy. Results from these novel elements will provide patients and clinicians with additional information regarding the impact of LXB on nighttime/daytime symptomatology. Support (if any) Jazz Pharmaceuticals

Narcolepsy is associated with disrupted nighttime sleep (DNS). Sodium oxybate (SXB; Xyrem®), administered twice nightly, is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years or older with narcolepsy. Recently, low-sodium oxybate (LXB, Xywav®; for people 7 years of age and older), which contains 92

Objective To compare intermediate-term risk of new-onset hypertension between normotensive patients with narcolepsy initiating sodium oxybate (SXB cohort) and those not initiating sodium oxybate (control cohort). Patients and Methods This retrospective cohort study used MarketScan administrative claims data from January 1, 2014, to February 29, 2020. Eligible patients were 18 years of age or older with continuous enrollment (≥180 days before and after cohort entry), had one or more narcolepsy claims or a prescription fill for sodium oxybate, had no history of hypertension or antihypertensive medication use, and had no use of sodium oxybate within 13 months before cohort entry. Patients in the SXB and control cohorts were matched 1:2 for the propensity score to balance baseline characteristics. End points were (1) a composite of new-onset hypertension diagnosis or antihypertensive medication initiation and (2) new-onset hypertension diagnosis. Patients were monitored for 180 days, until outcome occurrence, sodium oxybate discontinuation (SXB cohort), or sodium oxybate initiation (control cohort). Risk per 100 patients was reported; differences were evaluated using logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results The SXB and control cohorts included 954 and 1908 patients, respectively. Risk of new-onset hypertension diagnosis or antihypertensive medication initiation was higher in the SXB cohort than in the control cohort (6.60 vs 4.20 per 100 patients; OR, 1.61; 95% CI, 1.15 to 2.27). Risk of a new-onset hypertension diagnosis only in the SXB cohort was 0.94 per 100 patients and 0.52 per 100 patients in the control cohort (OR, 1.81; 95% CI, 0.73 to 4.46). Conclusion In this study, sodium oxybate use was associated with a new-onset hypertension diagnosis or antihypertensive medication initiation in normotensive patients with narcolepsy.

Abstract Introduction Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. To examine the long-term safety of LXB in this population, this post hoc analysis evaluated treatment-emergent adverse events (TEAEs) over time in a phase 3, double-blind, placebo-controlled, randomized withdrawal trial (NCT03533114), including its open-label extension period. Methods Participants were adults with idiopathic hypersomnia. TEAEs were analyzed across all study periods (open-label titration,10–14 weeks; stable-dose, 2 weeks; double-blind randomized withdrawal, 2 weeks; open-label extension, 24 weeks; safety follow-up, 2 weeks) in the analysis population (oxybate-naive participants who took ≥1 dose of study drug; N=148). Onset and duration of common TEAEs (≥5% of participants) were reported in the total population and by baseline medication group (treatment-naive, n=66; taking alerting agents [stimulants or wake-promoting agents], n=82). Duration was defined as the time from when a TEAE started until it was reported as ended. Results are presented using descriptive statistics. Results The majority of the most frequently reported TEAEs occurred within the first 5 weeks after study onset. In treatment-naive participants, the most common TEAEs (incidence; median duration) were nausea (n=13 [19.7%]; 7.5 days), headache (n=12 [18.2%]; 3.0 days), dizziness (n=11 [16.7%]; 4.0 days), anxiety (n=7 [10.6%]; 9.0 days), and decreased appetite (n=7 [10.6%]; 15.0 days). In participants taking alerting agents, the most common TEAEs were nausea (n=21 [25.6%]; 7.5 days), headache (n=15 [18.3%]; 2.0 days), vomiting (n=14 [17.1%]; 1.5 days), anxiety (n=10 [12.2%]; 28.0 days), insomnia (n=9 [11.0%]; 7.0 days), and tremor (n=9 [11.0%]; 11.0 days). Common TEAEs were of mild or moderate severity and infrequently led to study discontinuation (≤3.7% of participants each). Nine serious TEAEs occurred in 4/148 (2.7%) participants; none were considered related to study drug or led to study discontinuation. Conclusion In this study of LXB in participants with idiopathic hypersomnia, the common TEAEs (≥5% of participants) were consistent with the known safety profile of oxybate, peaked early (generally within 5 weeks), and were mild to moderate in severity, in both treatment-naive participants and participants taking alerting agents. Support (if any) Jazz Pharmaceuticals

Objective: The SEGUE study examines safety, tolerability, effectiveness, and treatment optimization in participants with narcolepsy transitioning from sodium oxybate (SXB) to lower-sodium oxybate (LXB; Xywav®). Background: LXB contains 92% less sodium than SXB and is approved for treating cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy (≥7 years of age). Design/Methods: Eligible participants in this ongoing, multicenter, open-label study (NCT04794491) are adults with narcolepsy (type 1 or 2) on an SXB stable dose (maximum 9 g/night; no single dose >6 g) and regimen (once, twice, or thrice nightly). After 2 weeks on SXB (baseline period), participants switch to the same LXB dose/regimen (intervention period; 6 weeks). If needed, LXB dose/regimen is titrated to optimize efficacy/tolerability. Assessments include the Patient Global Impression of Change (PGIc), forced preference questionnaire (FPQ), and ease of switching medication scale (EOSMS; all collected at end of treatment/early discontinuation). An interim analysis (first 24 completers) is reported. Results: Most participants were White (92%); 54% were female; mean (SD) age was 45.5 (16.20) years. Starting and ending (end of treatment/early discontinuation) median total nightly doses of LXB were both 9.0 g. Most participants took LXB twice nightly (88%). Twenty-two participants completed the transition period; mean (SD) time to optimized dose was 1.4 (1.56) days, and median (range) number of dose/regimen changes was 0.0 (0, 1). At end of treatment/early discontinuation, most reported improvement (very much/much/minimal; 57%) or no change (43%) in narcolepsy symptoms on the PGIc, preferred LXB over SXB on the FPQ (86%), and reported the transition was easy (easy/extremely easy/not difficult at all) on the EOSMS (91%). Most treatment-emergent adverse events reported were mild to moderate. Conclusions: Participants switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition was easy. Efficacy of oxybate treatment was maintained or improved, and most participants preferred LXB over SXB. Disclosure: Dr. Leary has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Leary has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Proper. Dr. Leary has stock in Jazz Pharmaceuticals. Dr. Kirby has received personal compensation for serving as an employee of Jazz Pharmaceuticals, Inc. Dr. Kirby has stock in Jazz Pharmaceuticals, Inc.. Dr. Skowronski has nothing to disclose. Mr. Xu has received personal compensation for serving as an employee of Jazz Pharmaceuticals Inc. Mr. Pfister has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Mr. Pfister has stock in Jazz Pharmaceuticals. Dr. Macfadden has received personal compensation for serving as an employee of Jazz pharma. Dr. Macfadden has stock in Jazz pharma.

Abstract Introduction Idiopathic hypersomnia (IH) is a rare neurologic disorder that can cause debilitating symptoms, including excessive daytime sleepiness, severe sleep inertia, prolonged nighttime sleep, long and unrefreshing naps, and cognitive dysfunction. Limited research has investigated the clinical burden associated with IH. This study compared the clinical profile of patients diagnosed with IH versus matched non-IH controls. Methods MarketScan® administrative claims were analyzed between December 2013 and February 2020. Eligible patients were aged ≥18 years upon cohort entry and had 365 days of continuous medical coverage (gaps ≤30 days allowed) before and after cohort entry. IH cases entered the cohort upon the first medical claim containing an IH diagnosis and without history of cataplexy. Non-IH controls were matched 5:1 to patients with IH on age, sex, region, payer type, and cohort entry date. Prevalence estimates of Clinical Classification System Multilevel (CCSM) categories and comorbid conditions during the 2-year study period were compared between cohorts using logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results The final cohorts included 11,428 and 57,138 patients with IH and non-IH controls, respectively. Approximately two-thirds of the sample was female (65.0%); median age was 45 years. Compared with non-IH controls, patients with IH experienced significantly higher prevalence of all CCSM categories. Prevalence estimates of conditions associated with sleep disorders, such as sleep apnea (OR: 26.1 [CI: 24.8, 27.6]), mood disorders (OR: 3.7 [CI: 3.6, 3.9]), and headache/migraine (OR: 2.9 [CI: 2.7, 3.0]), were higher among patients with IH. Similarly, cardiovascular conditions, including cardiovascular disease (OR: 2.2 [CI: 2.1, 2.4]), stroke (OR: 2.2 [CI: 2.0, 2.4]), major adverse cardiovascular events (OR: 2.2 [CI: 2.0, 2.4]), a composite of hypertension diagnosis or use of antihypertensive medications (OR: 2.0 [CI: 2.0, 2.1]), and heart failure (OR: 2.0 [CI: 1.8, 2.3]), were significantly more prevalent among patients with IH. Conclusion Patients with IH experience a significant burden of psychiatric and medical comorbidities, including acute and chronic cardiovascular illnesses. This is consistent with observations in other sleep disorders, namely, narcolepsy. Holistic treatment strategies for IH patients are needed, requiring careful consideration of patients’ overall clinical profile when selecting therapies. Support (if any) Jazz Pharmaceuticals.

Objective: This study compared intermediate-term risk (≤180 days) of new-onset hypertension among normotensive patients with narcolepsy initiating high-sodium oxybate (SXB cohort) with those not initiating high-sodium oxybate (controls). Background: High-sodium oxybate, a recommended narcolepsy treatment, contains a high-sodium content warning in its US Food and Drug Administration–approved labeling. The sodium-hypertension relationship is well established. Design/Methods: MarketScan® claims (1/2014 to 2/2020) were analyzed. Eligible adults had continuous enrollment and ≥1 narcolepsy claim or prescription for sodium oxybate. Patients with a history of hypertension, use of antihypertensives, and prior use of sodium oxybate were excluded. In a sensitivity analysis, patients with a history of cardiovascular disease (CVD) were also excluded. Two endpoints were assessed: 1) a composite of new-onset hypertension diagnosis or initiation of antihypertensive medication and 2) new-onset hypertension diagnosis alone. Propensity-score 1:2 matching was applied to balance baseline characteristics. Risk per 100 patients and adjusted odds ratios (ORs) were reported with 95% confidence intervals (CIs). Results: A total of 954 and 1906 patients were included in the SXB and control cohorts, respectively. Risk of the composite endpoint per 100 patients was higher in SXB (6.60) than control (4.20) cohorts (OR=1.61; 95% CI, 1.15–2.27); risk of new-onset hypertension per 100 patients was higher in SXB (0.94) than control (0.52) cohorts (OR=1.81; 95% CI, 0.73–4.46). In the sensitivity analysis, risk of the composite endpoint per 100 patients was higher in SXB (6.22) than control (4.06) cohorts (OR=1.57; 95% CI, 1.10–2.24); risk of new-onset hypertension per 100 patients was higher in SXB (0.89) than control (0.44) cohorts (OR=2.01; 95% CI, 0.75–5.36). Conclusions: This study showed increased risk of new-onset hypertension among normotensive patients with narcolepsy treated with sodium oxybate, even among patients without history of CVD. Clinicians should consider the cardiovascular risk associated with high-sodium oxybate. Disclosure: Dr. Ben-Joseph has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Ben-Joseph has stock in Jazz Pharmaceuticals. Virend Somers has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz Pharmaceuticals . Virend Somers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Respicardia. Virend Somers has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer . Virend Somers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Baker Tilly. The institution of Virend Somers has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sleep Number . Virend Somers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institutes Health . The institution of Virend Somers has received research support from National Institutes Health. The institution of Virend Somers has received research support from Sleep Number . Jed Black, MD has stock in Jazz Pharmaceuticals. Jed Black, MD has stock in . Dr. Dagostino has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz Pharmaceutical . Dr. Dagostino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Dagostino has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Exelixis. Dr. Dagostino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MEI Pharma. Dr. Dagostino has received research support from NIH. Mr. Saad has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Mr. Saad has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evidinno Outcomes Research Inc.. Mr. Saad has received stock or an ownership interest from Jazz Pharmaceuticals. Mat D. Davis has received personal compensation for serving as an employee of Teva pharmaceuticals. Mat D. Davis has received stock or an ownership interest from Teva Pharmaceuticals. Dr. Macfadden has received personal compensation for serving as an employee of Jazz pharma. Dr. Macfadden has stock in Jazz pharma. Dr. Mues has received personal compensation for serving as an employee of Aetion. Ms. Jackson has received personal compensation for serving as an employee of Aetion. Ms. Jackson has stock in Aetion. Dr. Ni has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Ni has stock in Jazz Pharmaceuticals. Dr. Cook has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Cook has stock in Jazz Pharmaceuticals. Miss Pitino has received personal compensation for serving as an employee of Aetion, Inc. Miss Pitino has stock in Aetion, Inc. Ms. Latimer has received personal compensation for serving as an employee of Aetion. Ms. Latimer has stock in Aetion. Ms. Dabrowski has received personal compensation for serving as an employee of Aetion, Inc.. Ms. Dabrowski has received stock or an ownership interest from AbbVie Inc.. Ms. Dabrowski has received stock or an ownership interest from BioMarin Pharmaceutical Inc.. Ms. Dabrowski has received stock or an ownership interest from CVS Health Corporation . Ms. Dabrowski has received stock or an ownership interest from Moderna Inc.. Ms. Dabrowski has received stock or an ownership interest from Walgreens Boots Alliance. Dr. White has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for JAZZ Pharmaceuticals.