Dataset Information

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial.

ABSTRACT:

Background

Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms.

Methods

573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ?30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing.

Results

Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ?30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p?0.001) and 25% for SXB6 g/night (p?0.001) versus 0.5% for placebo. Adverse events with an incidence ?5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema.

Conclusion

These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affords important benefits across multiple symptoms in subjects with fibromyalgia.

SUBMITTER: Spaeth M

PROVIDER: S-EPMC3371223 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial.

Spaeth Michael M Bennett Robert M RM Benson Beverly A BA Wang Y Grace YG Lai Chinglin C Choy Ernest H EH

Annals of the rheumatic diseases 20120131 6

<h4>Background</h4>Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms.<h4>Methods</h4>573 patients with fibromyalgia according ...[more]

PMID: 22294641

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Project description:The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM.This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ? 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ? 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum).Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9?±?10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9?±?8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ? 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ? 30% reduction in pain VAS and 69.7% achieved ? 30% reduction in FIQ total score at study endpoint.The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use.ClinicalTrials.gov NCT00423605.

Project description:BackgroundSodium oxybate has been recognized as a gold standard for the treatment of disrupted nighttime sleep due to narcolepsy. Its short half-life and immediate-release formulation require patients to awaken 2.5-4 h after their bedtime dose to take a second dose. A novel extended-release, once-nightly sodium oxybate formulation (ON-SXB; FT218) is under US Food and Drug Administration review for the treatment of adults with narcolepsy.ObjectiveA phase III trial of ON-SXB in individuals with narcolepsy type 1 (NT1) or 2 (NT2) [the REST-ON trial; NCT02720744] has been conducted and the primary results reported elsewhere. Secondary objectives from REST-ON were to assess the efficacy of ON-SXB on disrupted nighttime sleep; the results of this analysis are reported here.MethodsIn the double-blind, phase III REST-ON trial, patients aged ≥ 16 years were randomly assigned 1:1 to ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Secondary endpoints included polysomnographic measures of sleep stage shifts and nocturnal arousals and patient-reported assessments of sleep quality and refreshing nature of sleep at 6, 7.5, and 9 g; post hoc analyses included changes in time spent in each sleep stage, delta power, and assessments in stimulant-use subgroups for prespecified endpoints.ResultsIn total, 190 participants (n = 97, ON-SXB; n = 93, placebo) were included in the efficacy analyses. All three ON-SXB doses demonstrated a clinically meaningful, statistically significant decrease vs placebo in the number of transitions to wake/N1 from N1, N2, and rapid eye movement (REM) stages (all doses p < 0.001) and the number of nocturnal arousals (p < 0.05 ON-SXB 6 g; p < 0.001 7.5 and 9 g). Sleep quality and refreshing nature of sleep were significantly improved with all three ON-SXB doses vs placebo (p < 0.001). Post hoc analyses revealed a significant reduction in time spent in N1 (p < 0.05 ON-SXB 6 g; p < 0.001 7.5 and 9 g) and REM (all p < 0.001) and increased time spent in N3 with ON-SXB vs placebo (all p < 0.001), with a significant increase in delta power (p < 0.01 ON-SXB 6 g; p < 0.05 7.5 g; p < 0.001 9 g) and increased REM latency (ON-SXB 7.5 g vs placebo; p < 0.05). Significant improvements in disrupted nighttime sleep were observed regardless of concomitant stimulant use.ConclusionsThe clinically beneficial, single nighttime dose of ON-SXB significantly improved disrupted nighttime sleep in patients with narcolepsy.Clinical trial registrationClinicalTrials.gov NCT02720744.

Project description:Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient's life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia.

Dataset Information

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial.

Background

Methods

Results

Conclusion

Publications

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial.

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