Xywav (calcium/magnesium/potassium/sodium oxybates) / Jazz - LARVOL DELTA

SUNCET: Efficacy, Safety and Tolerability of Low Sodium Oxybate for Nocturnal Cluster Headache Attacks (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Leiden University Medical Center | Trial completion date: May 2028 ➔ May 2029 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Chronic Cluster Headache

XYRISE: A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Jazz Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

XYRISE: A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH (clinicaltrials.gov) - P3 | N=108 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals

New P3 trial • Narcolepsy • Sleep Disorder

Jazz Pharmaceuticals announced today it will present 21 abstracts at SLEEP 2026, the 40th annual meeting of the Associated Professional Sleep Societies, taking place June 14-17, 2026, in Baltimore. (Investing.com) - “The presentations include 11 late-breaking abstracts featuring clinical research and real-world evidence on Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution for treating narcolepsy and idiopathic hypersomnia, according to a press release statement…Key presentations include a post-hoc analysis of the DUET study examining sleep inertia in participants with narcolepsy taking Xywav. Two poster presentations will report analyses of the DUET study…Six poster presentations will feature findings from the LYRICAL study, examining treatment experience and dosing patterns of U.S. adults with idiopathic hypersomnia or narcolepsy taking Xywav.”

P4 data • Real-world evidence • Excessive Daytime Sleepiness • Narcolepsy

Low Sodium Oxybate in Patients With Idiopathic Hypersomnia (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Sleep Disorder

Changes in Self-Reported Cognitive Complaints, Functional Impairments, Work Productivity, and Symptom Severity in Participants With Narcolepsy After Treatment With Greater Than 9 Gram Dosages of Low-Sodium Oxybate in the DUET Study (AAN 2026) - P4 | "Objective To explore the impact of low-sodium oxybate (LXB; Xywav®) dosages >9 g/night on cognitive complaints, functional impairments, work productivity, and symptom severity in participants with narcolepsy who may benefit from higher LXB dosages, per investigator judgement...Treatment-emergent adverse events were consistent with known LXB safety profile. Conclusions Participants identified to optimize to LXB dosages >9 g/night experienced improvements (versus 9 g/night) in cognitive complaints, daily functioning, work productivity, and overall disease burden."

Narcolepsy • Sleep Disorder

Effectiveness and Safety of Low-Sodium Oxybate in Participants with Idiopathic Hypersomnia: Primary Results from the DUET Study. (PubMed, CNS Drugs) - P4 | "Individuals with idiopathic hypersomnia treated with open-label LXB showed improvements in subjective and objective measures of sleep and symptoms. Treatment-emergent adverse events were consistent with the known safety profile of LXB. This study supports the effectiveness of LXB in treating this condition with a 24-h burden of symptoms."

Journal • Fatigue • Narcolepsy • Pain • Sleep Disorder

Effects of low-sodium oxybate on diary-based sleep time in a clinical study in adults with idiopathic hypersomnia. (PubMed, Sleep Med) - P3 | "Open-label LXB treatment in adults with idiopathic hypersomnia was associated with reductions in 24-hour TST, nocturnal TST, and total nap duration."

Journal • Mood Disorders • Pain • Psychiatry • Sleep Disorder

Extended-release Sodium Oxybate in Children (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Stanford University | Initiation date: Jul 2025 ➔ Oct 2025

Trial initiation date • Narcolepsy • Sleep Disorder

Patient Perceptions of and Experiences with Risk Evaluation and Mitigation Strategies. (PubMed, Clin Pharmacol Ther) - "To understand patients' and caregivers' perception of and experiences with REMS programs with elements to assure safe use, we conducted semi-structured interviews from March 2022 to July 2023 with 135 patients or caregivers of patients who had used alemtuzumab (Lemtrada), ambrisentan (Letairis), clozapine (Clozaril), isotretinoin (Accutane), lenalidomide (Revlimid), pegvaliase (Palynziq), or sodium oxybate (Xyrem/Xywav). Among 135 participants, five key themes emerged: (1) Participants were knowledgeable about REMS-associated drug risks and requirements; (2) some participants had difficulty finding prescribers, particularly for clozapine; (3) administrative burdens related to REMS implementation were a source of frustration, with satisfaction higher when care coordination support was provided; (4) emotional and logistical challenges were identified with pregnancy- and clozapine-related testing; and (5) participants desired similar engagement around risks not..."

Journal

Clear-Brain: Stimulating Amyloid Clearance in Cerebral Amyloid Angiopathy (clinicaltrials.gov) - P2 | N=60 | Enrolling by invitation | Sponsor: Leiden University Medical Center | Not yet recruiting ➔ Enrolling by invitation | Trial completion date: Aug 2026 ➔ Sep 2027 | Trial primary completion date: Aug 2026 ➔ Sep 2027

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Mood Disorders • Psychiatry

Xywav: A Treatment Option for Idiopathic Hypersomnia in Down Syndrome. (PubMed, Cureus) - "Additionally, vulnerable populations, such as those with Down syndrome (DS), face further obstacles given the absence of therapeutic studies addressing IH in DS. This case presentation highlights the case of a 40-year-old female patient with DS who suffered from substantial hypersomnolence and had responded favorably to a supervised trial of Xywav (calcium, magnesium, potassium, or sodium oxybates), making this the first known case presentation to demonstrate an effective treatment strategy for this population."

Journal • CNS Disorders • Developmental Disorders • Excessive Daytime Sleepiness • Genetic Disorders • Sleep Disorder

Sleep Actigraphy in Participants With Narcolepsy or Idiopathic Hypersomnia Taking Low-Sodium Oxybate: Results From the DUET Study (WSS 2025) - P4 | "Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) was a phase 4, prospective, multicentre, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating effectiveness of low-sodium oxybate (LXB; Xywav®) on daytime and nighttime-related signs and symptoms in participants with narcolepsy or idiopathic hypersomnia... Based on actigraphy, participants with narcolepsy taking LXB showed decreased awakenings and WASO duration, suggesting less disrupted sleep with treatment, compared with BL (off-treatment). Participants with idiopathic hypersomnia taking LXB showed decreased total nocturnal sleep time, and fewer awakenings, which may reflect more restorative sleep. These results augment previously reported polysomnography findings in these participants, adding to the established effectiveness of LXB treatment for narcolepsy and idiopathic hypersomnia."

Narcolepsy • Sleep Disorder

Sleep Architecture With Low-Sodium Oxybate Treatment in Narcolepsy: Results From the DUET Study (WSS 2025) - P4 | "Introduction: Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) was a phase 4, prospective, multicentre, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating effectiveness of low-sodium oxybate (LXB, Xywav®) on daytime and nighttime-related signs and symptoms, including polysomnography (PSG)-based sleep architecture and disrupted nighttime sleep (DNS), in participants with narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia... Participants with narcolepsy taking open-label LXB experienced changes in duration and percentage of individual sleep stages, including increased N3 sleep and decreased N1 and REM, consistent with previous oxybate studies. Changes in N2 sleep and TST were negligible. Fewer shifts from deeper to lighter stages of sleep/wake were observed, suggesting improvement in DNS."

Narcolepsy • Sleep Disorder

Reduction in Sleep Inertia and Components of Daytime Sleepiness in Idiopathic Hypersomnia With Low-Sodium Oxybate Treatment in the Phase 4 DUET Study (WSS 2025) - P4 | "Low-sodium oxybate (LXB, Xywav®) is approved in the United States to treat idiopathic hypersomnia in adults and excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy... Compared with baseline, participants with idiopathic hypersomnia on optimised LXB treatment demonstrated reduced sleep inertia magnitude, less daytime sleepiness, and increased behavioural alertness."

P4 data • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Effect of Narcolepsy and Idiopathic Hypersomnia on Relationships: A Social Media Analysis (WSS 2025) - "Across all conversations that mentioned both sleeping and a partner, the most common topics identified were sleep medication usage, narcolepsy journey, Xyrem/Xywav, falling asleep, medical diagnosis journey, and vivid dreaming. These data suggest that nighttime sleep symptoms, including parasomnias, may be a source of concern within relationships of people with narcolepsy or IH. Sleepiness and bed sharing with a partner with narcolepsy or IH may cause relationship tension given the strong association with emotions with a negative connotation, such as anger and frustration."

Behavior Disorders • CNS Disorders • Mental Retardation • Narcolepsy • Psychiatry • Sleep Disorder

Sleep architecture with low-sodium oxybate treatment in idiopathic hypersomnia: results from the DUET study (WSS 2025) - P4 | "Introduction: Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) was a phase 4, prospective, multicentre, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating the effectiveness of low-sodium oxybate (LXB; Xywav®) treatment on daytime and nighttime-related signs and symptoms, including polysomnography (PSG)-based sleep architecture, in participants with idiopathic hypersomnia or narcolepsy... Participants with idiopathic hypersomnia treated with open-label LXB demonstrated reduced TST on ad libitum PSG versus BL, with corresponding increases in N3 sleep, decreases in N1, N2, and REM, and reduced stage shifts. These results suggest a potential correction of the underlying differences in sleep architecture between people with idiopathic hypersomnia and controls that have been described previously in a meta-analysis. These findings also represent the first evaluation of the impact of LXB treatment on PSG sleep..."

Narcolepsy • Sleep Disorder

Impact of Switching From High- to Low-Sodium Oxybate on Ambulatory Blood Pressure in People With Narcolepsy (WSS 2025) - P4 | "Materials and XYLO, an open-label, single-arm study (NCT05869773), evaluated people with narcolepsy aged 18−70 years with screening systolic blood pressure (SBP) 130−155 mmHg taking twice-nightly high-sodium oxybate (SXB; Xyrem®) 6–9 g for ≥6 weeks, switching to low-sodium oxybate (LXB; Xywav®) at the same dosage/regimen for ≈6 weeks. Switching from SXB to LXB reduced daily treatment-related sodium intake in participants with narcolepsy and was associated with clinically meaningful BP reductions, consistent with evidence on dietary sodium effects."

Cardiovascular • Hypertension • Narcolepsy • Sleep Disorder

Low Sodium Oxybate in Patients With Idiopathic Hypersomnia (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Sleep Disorder

Extended-release Sodium Oxybate in Children (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2027 ➔ Jul 2027 | Initiation date: Feb 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2027 ➔ Jun 2027

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Narcolepsy • Sleep Disorder

A Patient-centric Clinical Trial Design to Comprehensively Evaluate Low-Sodium Oxybate in People with Idiopathic Hypersomnia or Narcolepsy. (PubMed, Neurol Ther) - P4 | "Low-sodium oxybate (LXB; Xywav®) is approved to treat idiopathic hypersomnia in adults and excessive daytime sleepiness or cataplexy in individuals aged ≥ 7 years with narcolepsy...Using a patient-centric design aiming to address participants' burden and improve their study experience, the DUET study will fill critical idiopathic hypersomnia and narcolepsy evidence gaps pertaining to sleep architecture (e.g., disrupted nighttime sleep) and response to LXB treatment, as well as provide data on outcomes that are meaningful to patients. Graphical abstract available for this article."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

SUNCET: Low Sodium Oxybate as a Treatment for Nocturnal Cluster Headache (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Leiden University Medical Center

New P2 trial • Chronic Cluster Headache • Pain

A Study to Investigate the Effect of XYWAV on Sleepiness, Polysomnography, and Functional Outcomes in Participants With Idiopathic Hypersomnia or Narcolepsy (clinicaltrials.gov) - P4 | N=207 | Completed | Sponsor: Jazz Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Narcolepsy • Sleep Disorder

Drug-induced kidney stones: a real-world pharmacovigilance study using the FDA adverse event reporting system database. (PubMed, Front Pharmacol) - "The top 5 drugs most frequently linked to kidney stone cases were adalimumab (2,636 cases), infliximab (1,266 cases), interferon beta-1a (920 cases), sodium oxybate (877 cases), and teriparatide (836 cases). Notably, certain drugs like lansoprazole (ROR 7.2, 95% CI 6.62-7.84), Xywav (ROR 7.1, 95% CI 6.03-8.35), and teduglutide (ROR 5.54, 95% CI 4.83-6.36) showed significant risk signals...Our analysis of FAERS data revealed new risk signals for kidney stones not indicated in the labels of 33 drugs. Close monitoring is recommended when using these medications, and further research is needed to investigate the mechanisms behind drug-induced kidney stone formation."

Adverse events • Journal • Real-world evidence • Nephrology • Renal Calculi

A Switch Study From High-Sodium Oxybate to XYWAV to Evaluate Changes in Blood Pressure in Participants With Narcolepsy (clinicaltrials.gov) - P4 | N=160 | Completed | Sponsor: Jazz Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Narcolepsy • Sleep Disorder