A 12-week open-label, multicenter study evaluating the safety and patient-reported efficacy of sodium oxybate in patients with narcolepsy and cataplexy

Objective: This study aimed to evaluate safety and efficacy of sodium oxybate (SXB) titrated to effect. Methods: SXB-naive patients who had participated in a randomized SXB clinical trial and had not been titrated to adequate clinical effect were initiated on open-label SXB at 4.5 g/night and titrated in 1.5-g increments to 6, 7.5, or 9 g/night or down to 3 g/night, based on individual clinical response. Treatment was 12 weeks; safety was the primary outcome. Efficacy was evaluated using the Narcolepsy Symptom Assessment Questionnaire (NSAQ), a five-point scale (“much improved” to “much worse”) that assessed changes from baseline in specific symptoms. Response was defined as “much improved” or “somewhat improved” overall at weeks 6 and 12. Results: Of 202 patients, 171 (85%) completed treatment; final doses were 3 g (n = 5), 4.5 g (n = 29), 6 g (n = 80), 7.5 g (n = 66), and 9 g (n = 22). Adverse events (AEs) were reported in 114 patients (56%), serious AEs in five (2%). The most common AEs were nausea (10%), headache (7%), and dizziness (5%). Response rate was 92% at week 6 and 90% at week 12; most patients reported improvements in all individual symptoms. Overall, 60% of patients rated their symptoms at 12weeks as “much improved,” and this improvement was dose dependent. Conclusions: The SXB safety profile was consistent with parent trials. Ninety percent of patients reported improvements as measured by the NSAQ

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

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 affordsimportant benefits across multiple symptoms in subjects with fibromyalgia

Evaluation of qualityof-life in patients with narcolepsy treated with sodium oxybate : use of the 36-item short-form health survey in a clinical trial

Introduction The present post hoc analysis was designed to evaluate health-related quality of life (HRQoL) using the 36-item Short Form Health Status Survey (SF-36) during an 8-week trial of sodium oxybate (SXB). Methods SF-36 was assessed in a phase 3 placebo-controlled trial in patients with narcolepsy (N = 228) randomized to placebo or SXB in doses of 4.5, 6, or 9 g nightly for 8 weeks. Changes from baseline in SF-36 (last observation carried forward) were compared between SXB and placebo, and effect sizes (ES) were estimated. Results Baseline SF-36 values were lower than normative values for the US general population. After 8 weeks of treatment, mean (±standard deviation) improvement from baseline on the Physical Component Summary (PCS) was significantly greater with SXB 9 g/night than placebo (6.3 ± 9.1 vs. 1.5 ± 6.2; p = 0.005), with moderate ES; no significant difference was found between the SXB and placebo groups on the Mental Component Summary. SXB 9 g/night resulted in significantly (p < 0.05) greater improvements than placebo in Physical Functioning (4.4 ± 9.2 vs. 1.0 ± 8.0), General Health (GH; 3.1 ± 7.0 vs. 0.4 ± 6.8), and Social Functioning (6.8 ± 16.8 vs. 1.1 ± 9.6). All SXB doses resulted in significant improvement (p < 0.05) relative to placebo for Vitality, with moderate ES. No significant differences versus placebo were observed for Role–Physical, Role–Emotional, or Mental Health domains. Conclusion Treatment with SXB was associated with a dose-dependent improvement in HRQoL, with the 9-g nightly dose demonstrating a positive impact on PCS and individual SF-36 domains of Vitality, GH, and Physical and Social Functioning

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease : Final Results From the International Compassionate Use Program

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy results were consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose. (C) 2016 American Society for Blood and Marrow Transplantation.Peer reviewe

Criteria for Gauging Response to Sodium Oxybate for Narcolepsy

Our objective was to define responder criteria using an anchor-based approach for frequency of cataplexy attacks and excessive daytime sleepiness in narcolepsy patients undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo-controlled, double blind, multi-center 4-week and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analyzed using receiver operator characteristics analysis. Percent change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared to Clinical Global Impression of Change ratings, used as the anchor to define true response. Participants (n=336) were 39% male, 89% white, with a mean age of 41.5 (15.3), reporting a median of 20.5 cataplexy attacks per week and a mean Epworth Sleepiness score of 17.5 at baseline. A majority (51%) were much or very much improved based on Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%) supported response definition thresholds of 46% and 12%, respectively. Classification using either response definition agreed with the anchor for approximately 71% of participants. Cataplexy response definition was more sensitive (Cataplexy=0.77, ESS=0.69) while sleepiness was more specific (Cataplexy=0.66, ESS=0.75). Both responder definitions showed a dose response relationship with sodium oxybate demonstrating their validity using an external criterion. Weekly cataplexy attacks and ESS can be used to help document clinical response to narcolepsy treatment using criteria of 46% and 12% reductions, respectively

Evaluation of Quality of Life in Patients With Narcolepsy Treated With Sodium Oxybate: Use of the 36-Item Short-Form Health Survey in a Clinical Trial

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-016-0053-5">https://link.springer.com/article/10.1007/s40120-016-0053-5</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD

International audienc