The Experts below are selected from a list of 1605 Experts worldwide ranked by ideXlab platform
Jed Black - One of the best experts on this subject based on the ideXlab platform.
-
The Xyrem^® (Sodium Oxybate) Risk Evaluation and Mitigation Strategy (REMS) Program in the USA: Results From 2016 to 2017
Drugs - Real World Outcomes, 2021Co-Authors: Michael J. Strunc, Jed Black, Prasheel Lillaney, Judi Profant, Sherice Mills, Shay Bujanover, Michael J. ThorpyAbstract:Background Sodium Oxybate, which is approved for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy, is available in the USA only through the restricted-distribution Xyrem^® Risk Evaluation and Mitigation Strategy Program (Xyrem REMS Program, XRP). The XRP requires prescriber enrollment and certification, patient enrollment, and prescriber attestation of patient counseling. Sodium Oxybate is dispensed only by the certified pharmacy. After pharmacist/patient counseling, Sodium Oxybate is shipped only to enrolled patients, with documentation of safe use. Documentation of enrollments, prescriptions, counseling, shipments, and adverse events in a central database, and risk management reporting of any suspicion of abuse, misuse, or diversion, ensure provider notification and facilitate monitoring. Objective This analysis reports data from the XRP regarding assessment of the risks of serious adverse outcomes that may result from inappropriate prescribing, abuse, misuse, and diversion. Methods Data collected from December 2016 to December 2017 were analyzed. Results Prescriptions were from enrolled prescribers ( n = 4524); 17,037 patients received one or more shipment of Sodium Oxybate. No patients were shipped Sodium Oxybate under more than one name/identifier or after being disenrolled; no individual patient had overlapping active prescriptions. Sodium Oxybate was dispensed in 146,426 shipments containing 375,173 bottles; of those, 13 shipments (0.009%) and 26 bottles (0.007%) were lost in delivery and not recovered. Notifications regarding potential abuse ( n = 31), misuse ( n = 343), or diversion ( n = 22) were discussed with prescribers. Most patients and prescribers were aware of the main safety risks of Sodium Oxybate. Conclusions The XRP maintains controlled access to Sodium Oxybate; additional prescriber education on safety risks may be warranted.
-
treatment of paediatric narcolepsy with Sodium Oxybate a double blind placebo controlled randomised withdrawal multicentre study and open label investigation
The Lancet Child & Adolescent Health, 2018Co-Authors: Giuseppe Plazzi, Jed Black, Michel Lecendreux, Yves Dauvilliers, Chad Ruoff, Carol L Rosen, R Parvataneni, D Guinta, Youyu Grace Wang, Emmanuel MignotAbstract:Summary Background Narcolepsy is a lifelong neurological disorder with onset commonly in childhood or adolescence. No drugs are indicated for cataplexy and excessive daytime sleepiness in paediatric patients with narcolepsy. Sodium Oxybate is approved for use in adult patients with excessive daytime sleepiness or cataplexy, or both, in narcolepsy. We aimed to examine the safety and efficacy of Sodium Oxybate oral solution treatment in children and adolescents who have narcolepsy with cataplexy. Methods This was a prospective, double-blind, placebo-controlled, randomised-withdrawal, multisite study and open-label investigation done at 30 sites in five countries (USA, Finland, France, Italy, and the Netherlands). Eligible participants were aged 7–16 years at screening, had narcolepsy with cataplexy, and were either being treated with Sodium Oxybate or were Sodium Oxybate-naive at entry. Sodium Oxybate-naive participants were titrated to an optimal dose. Participants were randomly assigned (1:1) with a dynamic randomisation algorithm to receive placebo or to remain on Sodium Oxybate for 2 weeks; they then entered an open-label Sodium Oxybate treatment period for a total study duration of up to 1 year. Random assignment to placebo was discontinued if early efficacy was shown in the preplanned interim analysis of the primary efficacy endpoint, which was change in weekly number of cataplexy attacks. Participants entering the study after the interim analysis would then be assigned to receive open-label Sodium Oxybate for 2 weeks. The primary analysis of efficacy and safety included data collected until the cutoff date of Feb 10, 2017. The efficacy population consisted of all participants randomly assigned to receive an intervention who completed at least 5 days of dosing in the double-blind treatment period, and the safety population consisted of all participants who took the study drug, including open-label Sodium Oxybate. This study is registered with ClinicalTrials.gov, number NCT02221869. Findings Between Oct 1, 2014, and Feb 10, 2017, we enrolled 106 participants, and 104 took the study drug (the safety population). 96 (92%) of these participants completed the stable-dose period, of whom 63 participants (the efficacy population) were randomly assigned to receive Sodium Oxybate (n=31) or placebo (n=32) for 2 weeks. A preplanned interim analysis of the primary endpoint showed efficacy (p=0·0002), resulting in discontinuation of the placebo arm following guidance from the data safety monitoring board; 33 participants then received Sodium Oxybate on an open-label basis during the double-blind period. Participants who were randomly assigned to receive placebo and who were withdrawn from Sodium Oxybate (32 [51%] of 63 patients) had increased weekly cataplexy attacks (median increase of 12·7 attacks per week [Q1, Q3=3·4, 19·8]) when compared with those randomly assigned to continue treatment with Sodium Oxybate (median increase of 0·3 attacks per week [–1·0, 2·5]; p 5%) adverse events were enuresis (15 [21%] of 72 Sodium Oxybate-naive participants vs four [13%] of 32 participants taking Sodium Oxybate at study entry), nausea (16 [22%] vs two [6%]), vomiting (15 [21%] vs two [6%]), headache (13 [18%] vs four [13%]), decreased weight (11 [15%] vs one [3%]), decreased appetite (eight [11%] vs none), nasopharyngitis (seven [10%] vs none), and dizziness (five [7%] vs 1 [3%]). Two serious adverse events (one event of severe acute psychosis and one event of moderate suicidal ideation) were reported, and both were considered to be related to the study drug. There were no reported deaths. Interpretation These results support the clinical efficacy of Sodium Oxybate for the treatment of both excessive daytime sleepiness and cataplexy in narcolepsy in children. The safety profile of Sodium Oxybate was consistent with that observed in adult patients. Funding Jazz Pharmaceuticals.
-
effect of Sodium Oxybate on disrupted nighttime sleep in patients with narcolepsy
Journal of Sleep Research, 2017Co-Authors: Thomas Roth, Yves Dauvilliers, D Guinta, Sarah Alvarezhorine, Efim Dynin, Jed BlackAbstract:This post hoc analysis evaluated the dose-related effects of Sodium Oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of Sodium Oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or Sodium Oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses. Relative to baseline, significant dose-dependent reductions in the number of shifts per hour from Stages N2/3/rapid eye movement and Stages N2/3 to Stage N1/Wake were observed at week 8 with Sodium Oxybate (P < 0.05); Sodium Oxybate 6- and 9-g doses also resulted in similar reductions in shifts per hour of rapid eye movement to Stage N1/Wake (both P < 0.05). Across all shift categories, the shift reductions with Sodium Oxybate 9 g were significantly greater than those observed with placebo (P < 0.05). Improvements from baseline in reported sleep quality were significantly greater with Sodium Oxybate 4.5 and 9 g at week 8 (P < 0.05). Correlations between change from baseline in number of shifts per hour to Stage N1/Wake and cataplexy frequency, patient-reported nocturnal sleep quality, and excessive daytime sleepiness assessed using the Epworth Sleepiness Scale were numerically highest for the Sodium Oxybate 9-g dose across all sleep stage shift categories. In these patients with narcolepsy, Sodium Oxybate showed improvements in the sleep continuity and nocturnal sleep quality that are characteristic of disrupted nighttime sleep (ClinicalTrials.gov identifier NCT00049803).
-
Effect of Sodium Oxybate on disrupted nighttime sleep in patients with narcolepsy
Journal of Sleep Research, 2017Co-Authors: Thomas Roth, Yves Dauvilliers, D Guinta, Efim Dynin, Sarah Alvarez-horine, Jed BlackAbstract:This post hoc analysis evaluated the dose-related effects of Sodium Oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of Sodium Oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or Sodium Oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses. Relative to baseline, significant dose-dependent reductions in the number of shifts per hour from Stages N2/3/rapid eye movement and Stages N2/3 to Stage N1/Wake were observed at week 8 with Sodium Oxybate (P
-
the nightly administration of Sodium Oxybate results in significant reduction in the nocturnal sleep disruption of patients with narcolepsy
Sleep Medicine, 2009Co-Authors: Jed Black, Daniel Pardi, Carl S Hornfeldt, Neil InhaberAbstract:Abstract Background Previous studies indicate that nightly Sodium Oxybate administration reduces nocturnal sleep disruption in narcolepsy. The present study provided an opportunity to further characterize these sleep-related effects in patients with narcolepsy during treatment with Sodium Oxybate as monotherapy or in combination with modafinil. Methods This double-blind, placebo-controlled study enrolled 278 patients with narcolepsy taking modafinil 200–600 mg daily for the treatment of excessive daytime sleepiness (EDS). Following a baseline polysomnogram (PSG) and Maintenance of Wakefulness Test (MWT), patients were randomized to receive treatment with: (1) placebo, (2) Sodium Oxybate, (3) modafinil, or (4) Sodium Oxybate + modafinil. PSGs and MWTs were repeated after 4 and 8 weeks. Other efficacy measures included Epworth Sleepiness Scale scores and daily diary recordings. Results After 8 weeks, significant changes in sleep architecture among patients receiving Sodium Oxybate and Sodium Oxybate/modafinil included a median increase in Stage 3 and 4 sleep (43.5 and 24.25 min, respectively) and delta power and a median decrease in nocturnal awakenings (6.0 and 9.5, respectively). No significant changes in PSG parameters were noted in patients treated with placebo or modafinil alone. Conclusions In addition to its established efficacy for the treatment of cataplexy and EDS, nightly Sodium Oxybate administration significantly reduces measures of sleep disruption and significantly increases slow-wave sleep in patients with narcolepsy.
Daniel Pardi - One of the best experts on this subject based on the ideXlab platform.
-
the nightly administration of Sodium Oxybate results in significant reduction in the nocturnal sleep disruption of patients with narcolepsy
Sleep Medicine, 2009Co-Authors: Jed Black, Daniel Pardi, Carl S Hornfeldt, Neil InhaberAbstract:Abstract Background Previous studies indicate that nightly Sodium Oxybate administration reduces nocturnal sleep disruption in narcolepsy. The present study provided an opportunity to further characterize these sleep-related effects in patients with narcolepsy during treatment with Sodium Oxybate as monotherapy or in combination with modafinil. Methods This double-blind, placebo-controlled study enrolled 278 patients with narcolepsy taking modafinil 200–600 mg daily for the treatment of excessive daytime sleepiness (EDS). Following a baseline polysomnogram (PSG) and Maintenance of Wakefulness Test (MWT), patients were randomized to receive treatment with: (1) placebo, (2) Sodium Oxybate, (3) modafinil, or (4) Sodium Oxybate + modafinil. PSGs and MWTs were repeated after 4 and 8 weeks. Other efficacy measures included Epworth Sleepiness Scale scores and daily diary recordings. Results After 8 weeks, significant changes in sleep architecture among patients receiving Sodium Oxybate and Sodium Oxybate/modafinil included a median increase in Stage 3 and 4 sleep (43.5 and 24.25 min, respectively) and delta power and a median decrease in nocturnal awakenings (6.0 and 9.5, respectively). No significant changes in PSG parameters were noted in patients treated with placebo or modafinil alone. Conclusions In addition to its established efficacy for the treatment of cataplexy and EDS, nightly Sodium Oxybate administration significantly reduces measures of sleep disruption and significantly increases slow-wave sleep in patients with narcolepsy.
-
Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical Sodium Oxybate (Xyrem): differences in characteristics and misuse.
Drug and alcohol dependence, 2009Co-Authors: Lawrence P Carter, Daniel Pardi, Jane Gorsline, Roland R GriffithsAbstract:There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical Sodium Oxybate. Gamma-hydroxybutyrate Sodium and Sodium Oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem (Sodium Oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes. This review highlights important differences between illicit GHB and Sodium Oxybate with regard to their relative abuse liability, which includes the likelihood and consequences of abuse. Data are summarized from the scientific literature; from national surveillance systems in the U.S., Europe, and Australia (for illicit GHB); and from clinical trials and post-marketing surveillance with Sodium Oxybate (Xyrem). In the U.S., the prevalence of illicit GHB use, abuse, intoxication, and overdose has declined from 2000, the year that GHB was scheduled, to the present and is lower than that of most other licit and illicit drugs. Abuse and misuse of the pharmaceutical product, Sodium Oxybate, has been rare over the 5 years since its introduction to the market, which is likely due in part to the risk management program associated with this product. Differences in the accessibility, purity, dosing, and misuse of illicit GHB and Sodium Oxybate suggest that risks associated with illicit GHB are greater than those associated with the pharmaceutical product Sodium Oxybate.
-
Sodium Oxybate for excessive daytime sleepiness in parkinson disease an open label polysomnographic study
JAMA Neurology, 2008Co-Authors: William G Ondo, Todd J Swick, Thomas Perkins, Keith L Hull, Ernesto J Jimenez, Tippy S Garris, Daniel PardiAbstract:Background Many patients with Parkinson disease (PD) have excessive daytime sleepiness and numerous nocturnal sleep abnormalities. Objective To determine the safety and efficacy of the controlled drug Sodium Oxybate in a multicenter, open-label, polysomnographic study in subjects with PD and sleep disorders. Design, Setting, and Patients Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleep-disordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off (“off”) PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started Sodium Oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an off-medication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD). Results We enrolled 38 subjects. At screening, 8 had sleep apnea (n = 7) or depression (n = 1). Twenty-seven of 30 subjects completed the study. Three dropped out owing to dizziness (n = 3) and concurrent depression (n = 1). The mean dose of Sodium Oxybate was 7.8 (1.7) g per night. The ESS score improved from 15.6 (4.2) to 9.0 (5.0) ( P P P P = .005). Changes in off-medication UPDRS scores were not significant, from 28.4 (10.3) to 26.2 (9.6). Conclusion Nocturnally administered Sodium Oxybate improved excessive daytime sleepiness and fatigue in PD. Trial Registration clinicaltrials.gov Identifier:NCT00641186
-
γ-Hydroxybutyrate/Sodium Oxybate
CNS Drugs, 2006Co-Authors: Daniel Pardi, Jed BlackAbstract:γ-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium Oxybate is the Sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA_B receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO_2 and H_2O through the tricarboxylic acid cycle (Krebs cycle). Sodium Oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, Sodium Oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to nighttime Sodium Oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
-
Sodium Oxybate neurobiology and clinical efficacy
Future Neurology, 2006Co-Authors: Daniel Pardi, Jed BlackAbstract:Sodium Oxybate is the Sodium salt of γ-hydroxybutyrate (GHB), an endogenous short-chain fatty acid that is speculated to function as a neurotransmitter in the mammalian CNS. Pharmacodynamic effects of exogenously-administered Sodium Oxybate may include modulating the release of neurotransmitters, including γ-aminobutyric acid, dopamine, endogenous opioids and serotonin, and stimulating release of growth hormone. It is rapidly absorbed, with approximately 25% bioavailability and a plasma half-life of 40–60 min, necessitating twice-nightly dosing. Sodium Oxybate is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy, and has been shown to improve disrupted night-time sleep and increase Stage 3 and 4 (slow-wave restorative) sleep in this patient population. The most common adverse events reported in clinical trials in patients with narcolepsy include headache, nausea, dizziness, nasopharyngitis, somnolence, vomiting and urinary incontinence.
Steven J Frucht - One of the best experts on this subject based on the ideXlab platform.
-
A novel therapeutic agent, Sodium Oxybate, improves dystonic symptoms via reduced network-wide activity
Scientific Reports, 2018Co-Authors: Kristina Simonyan, Steven J Frucht, Andrew Blitzer, Azadeh Hamzehei Sichani, Anna F RumbachAbstract:Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, Sodium Oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of Sodium Oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that Sodium Oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that Sodium Oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.
-
an open label study of Sodium Oxybate in spasmodic dysphonia
Laryngoscope, 2017Co-Authors: Anna F Rumbach, Andrew Blitzer, Steven J Frucht, Kristina SimonyanAbstract:Objectives/Hypothesis Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Study Design Open-label study. Methods We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of Sodium Oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Results Sodium Oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium Oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Conclusions Our study demonstrated that Sodium Oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of Sodium Oxybate in SD and SD/VT may be linked to that of alcohol, and as such, Sodium Oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. Level of Evidence 4 Laryngoscope, 2016
-
Case Reports Long-term Effect of Sodium Oxybate (XyremH) in Spasmodic Dysphonia with Vocal Tremor
2016Co-Authors: Kristina Simonyan, Steven J FruchtAbstract:Background: Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. Case Report: We report a case of a female with SD and VT who became symptom-free for 10 months after the intake of a single dose of Sodium Oxybate (XyremH). The long-term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network. Discussion: Our case demonstrates that the novel treatment of Sodium Oxybate may hold promise for SD patients, especially those who have associated VT
-
Long-term Effect of Sodium Oxybate (Xyrem®) in Spasmodic Dysphonia with Vocal Tremor.
Tremor and other hyperkinetic movements (New York N.Y.), 2013Co-Authors: Kristina Simonyan, Steven J FruchtAbstract:Background: Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. Case Report: We report a case of a female with SD and VT who became symptom‐free for 10 months after the intake of a single dose of Sodium Oxybate (Xyrem®). The long‐term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network. Discussion: Our case demonstrates that the novel treatment of Sodium Oxybate may hold promise for SD patients, especially those who have associated VT.
-
a patient with intractable posthypoxic myoclonus lance adams syndrome treated with Sodium Oxybate
Anaesthesia and Intensive Care, 2009Co-Authors: R Arpesella, C Dallocchio, C Arbasino, R Imberti, R Martinotti, Steven J FruchtAbstract:Posthypoxic myoclonus is a rare and devastating complication of near-fatal cardiopulmonary arrest. Despite treatment with available anti-myoclonic agents, some patients may recover cognitively but remain completely disabled by severe myoclonus. We report a 16-year-old patient with severe treatment-refractory posthypoxic myoclonus, which improved markedly with administration of the drug Sodium Oxybate.
Martin B Scharf - One of the best experts on this subject based on the ideXlab platform.
-
Sodium Oxybate for Narcolepsy
Expert review of neurotherapeutics, 2006Co-Authors: Martin B ScharfAbstract:Sodium Oxybate (Xyrem), also known as gamma-hydroxybutyric acid, is the only therapeutic specifically approved in the USA for the treatment of cataplexy in narcolepsy. The US FDA has recently expanded its indication to include excessive daytime sleepiness associated with narcolepsy. In contrast to the antidepressants and stimulants commonly used to treat the disorder, Sodium Oxybate is the only compound that addresses both sets of symptoms and, when used properly, is less likely to lead to the development of tolerance and other undesirable side effects. In this review, the results of clinical trials and the place of Sodium Oxybate in narcolepsy treatment are discussed.
-
the pharmacokinetics of Sodium Oxybate oral solution following acute and chronic administration to narcoleptic patients
The Journal of Clinical Pharmacology, 2004Co-Authors: Lowell A Borgen, Richard A Okerholm, Allen A Lai, Martin B ScharfAbstract:This trial was conducted to evaluate the pharmacokinetics and safety of a Sodium Oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically confirmed narcolepsy. The patients were administered a bedtime dose of 4.5 g of Sodium Oxybate while in a sleep research center. They were subsequently treated with Sodium Oxybate at the nightly dose of 4.5 g for 8 weeks. The patients then returned to the sleep center and were again treated with the 4.5-g Sodium Oxybate dose at bedtime. Blood samples (5 mL) were collected at 18 time points before and up to 7 hours after both the first dose of Sodium Oxybate and following 8 weeks of dosing. Plasma samples were analyzed for Oxybate con tent by a validated liquid chromatography/tandem mass spectrometry (LC/MS/ MS) method. Noncompartmental methods were applied in the determination of pharmacokinetic parameters from each patient's plasma Oxybate concentration versus time curve. No serious adverse events were recorded, and all patients completed the study. Headache, enuresis, and leg cramps were reported as adverse experiences. With both acute and chronic dosing, Sodium Oxybate was rapidly absorbed and eliminated with an apparent half-life of about 40 minutes. The only changes observed in the kinetics of Oxybate after 8 weeks of treatment were a 13% and 16% increase in peak concentration (C m a x ) and systemic exposure (AUC), respectively. The pharmacokinetics of Sodium Oxybate in narcoleptic patients were not changed in any clinically significant manner when the drug was chronically administered. The drug was well tolerated.
-
the effects of Sodium Oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia
The Journal of Rheumatology, 2003Co-Authors: Martin B Scharf, Margaret Baumann, David V BerkowitzAbstract:OBJECTIVE: Fibromyalgia (FM) is associated with the sleep phenomenon of alpha intrusion, and with low growth hormone secretion. Sodium Oxybate has been shown to increase both slow-wave sleep and growth hormone levels. This double blind, randomized, placebo controlled crossover trial was conducted to evaluate the effects of Sodium Oxybate on the subjective symptoms of pain, fatigue, and sleep quality and the objective polysomnographic (PSG) sleep variables of alpha intrusion, slow-wave (stage 3/4) sleep, and sleep efficiency in patients with FM. METHODS: Patients received either 6.0 g/day Sodium Oxybate or placebo for 1 month, with an intervening 2 week washout period. Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements from daily diary entries. Safety measures included clinical laboratory values, vital signs, and adverse events. RESULTS: Twenty-four female patients were included in the study; 18 completed the trial. TPI was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p = 0.0079). Six of the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with Sodium Oxybate, compared with 6% to 10% relief with placebo (p
Kristina Simonyan - One of the best experts on this subject based on the ideXlab platform.
-
A novel therapeutic agent, Sodium Oxybate, improves dystonic symptoms via reduced network-wide activity
Scientific Reports, 2018Co-Authors: Kristina Simonyan, Steven J Frucht, Andrew Blitzer, Azadeh Hamzehei Sichani, Anna F RumbachAbstract:Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, Sodium Oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of Sodium Oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that Sodium Oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that Sodium Oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.
-
an open label study of Sodium Oxybate in spasmodic dysphonia
Laryngoscope, 2017Co-Authors: Anna F Rumbach, Andrew Blitzer, Steven J Frucht, Kristina SimonyanAbstract:Objectives/Hypothesis Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Study Design Open-label study. Methods We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of Sodium Oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Results Sodium Oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium Oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Conclusions Our study demonstrated that Sodium Oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of Sodium Oxybate in SD and SD/VT may be linked to that of alcohol, and as such, Sodium Oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. Level of Evidence 4 Laryngoscope, 2016
-
Case Reports Long-term Effect of Sodium Oxybate (XyremH) in Spasmodic Dysphonia with Vocal Tremor
2016Co-Authors: Kristina Simonyan, Steven J FruchtAbstract:Background: Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. Case Report: We report a case of a female with SD and VT who became symptom-free for 10 months after the intake of a single dose of Sodium Oxybate (XyremH). The long-term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network. Discussion: Our case demonstrates that the novel treatment of Sodium Oxybate may hold promise for SD patients, especially those who have associated VT
-
Long-term Effect of Sodium Oxybate (Xyrem®) in Spasmodic Dysphonia with Vocal Tremor.
Tremor and other hyperkinetic movements (New York N.Y.), 2013Co-Authors: Kristina Simonyan, Steven J FruchtAbstract:Background: Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. Case Report: We report a case of a female with SD and VT who became symptom‐free for 10 months after the intake of a single dose of Sodium Oxybate (Xyrem®). The long‐term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network. Discussion: Our case demonstrates that the novel treatment of Sodium Oxybate may hold promise for SD patients, especially those who have associated VT.
