Sodium oxybate

Articles · Lactation Safety Information · New Medicines ·

410918008

Articles

Lactation Safety Information

Dexamfetamine
Sodium salt of a naturally occurring substance found in breast milk
Very limited published evidence of safety
Monitor infant for excessive drowsiness
Avoid breastfeeding from time of the first dose to 4 to 6 hours after the second dose
3rd January 2018

New Medicines

Xyrem (EU), Rekinla · Narcolepsy with cataplexy in children and adolescents aged 7 years and older

Information

Xyrem (EU), Rekinla
Licence extension / variation
UCB Pharma
Jazz Pharmaceuticals

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Oct 18 · US FDA approves sodium oxybate (Xyrem®) oral solution for treatment of cataplexy or excessive daytime sleepiness in paediatric narcolepsy patients [9].
Aug 18 · Sodium oxybate listed in CHMP list of medicines under evaluation; assume this indication [8].
Dec 17 · US filing now planned for mid-2018 [5].
Dec 16 · Enrolment complete in PIII study. US filing expected late 2017 [4].
Jun 16 · Filed in US Q2 18 [7].

Category

Dopamine agonist
Prevalence is estimated as 25 per 100,000 in Caucasian populations. Age of onset is typically around adolescence. A smaller number of cases presents at around 35 years. Less than 5% of narcolepsy with cataplexy occurs in children. One study found that it was often linked to complex movement disorders. It is possible that incidence statistics would increase if diagnostic features were recognised at an earlier age [2].
Narcolepsy with cataplexy in children and adolescents aged 7 years and older
Oral

Trial or other data

May 18 · PIII EXPRESS study published in The Lancet Child & Adolescent Health (NCT02221869). 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 Participants who were randomly assigned to receive placebo and who were withdrawn from sodium oxybate (32 [51%] of 63 patients) had increased weekly cataplexy attacks (median increase of 12·7 attacks per week [Q1, Q3=3·4, 19·8]) when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<0·0001) [10].
Sep 17 · PIII study (NCT02221869) still expects to complete data collection Nov 17 [6].
Oct 16 · PIII study (NCT02221869) is ongoing and has completed patient recruitment [3].
Sep 14 · PIII study (NCT02221869) to assess efficacy and safety of Xyrem in97 pediatrics subjects with narcolepsy that includes cataplexy starts. Study sites include the US, Finland, France and the netherlands. Primary outcomes are change in weekly number of cataplexy attacks at 2 weeks and adverse events; collection of these data should complete Nov 17 [3].

Excessive daytime sleepiness and cataplexy in patients with narcolepsy aged 16 or older

Information

New formulation
Avadel Pharmaceuticals
Avadel Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Sodium oxybate (GABA B receptor agonist) in a controlled release formulation using Micropump® technology
Prevalence is estimated as 25 per 100,000 in Caucasian populations. Age of onset is typically around adolescence. A smaller number of cases presents at around 35 years. Over 95% of narcolepsy with cataplexy occurs in adults [1].
Excessive daytime sleepiness and cataplexy in patients with narcolepsy aged 16 or older
Oral

Evidence based evaluations

Hopveus · Alcohol dependence

Information

Hopveus
New formulation
D&A Pharma
Not Known

Development and Regulatory status

Not recommended for approval (Negative opinion)
Not recommended for approval (Negative opinion)
None
Apr 20 · After re-examination, the EMA recommendation for refusal has been confirmed. As the data submitted were insufficient to establish effectiveness, the Agency’s opinion was that the benefits of the medicine did not outweigh its risks. These concerns were not addressed by further restricting use (to treatment of alcohol withdrawal syndrome and maintenance of abstinence under careful medical supervision along with psychotherapy and social rehabilitation), as the company had proposed, and the refusal was therefore confirmed [6].
Nov 19 · The company has asked for a re-examination of the CHMP negative opinion [5]. They now have 60 days to submit their grounds for re-examination (which should not include new data); once these have been received by the EMA, the CHMP must deliver a final verdict within 60 days.
Oct 19 · CHMP negative opinion recommending refusal of a licence for treatment of alcohol dependence. Although some of the studies presented suggested sodium oxybate could be effective in treatment, this was not conclusively demonstrated, and the Agency was concerned because there were several drawbacks in the design and analysis of these studies that could have affected the results. In addition there were concerns regarding its misuse and abuse potential [2].

Category

Attaches to receptors on nerve cells of the brain and spinal cord for gamma-aminobutyric acid (GABA), leading to a calming of the activity of these cells. Oral immediate-release formulation.
Alcohol dependence affects 4% of people aged between 16 and 65 in England (6% of men and 2% of women). More than 24% of the English population consume alcohol in a way that is potentially or actually harmful to their health or well-being. In 2012 there were 6,490 alcohol-related deaths. This is a 19% increase from 2001 but a 4% decrease from 2011 [1].
Alcohol dependence
Oral

Trial or other data

Sep 13 · Data from a number of international clinical trials (including GATE 1, GATE 2 and GUM) will be used to support EU regulatory applications. The GATE trials have been conducted in Germany, Austria, Italy and Poland. The GUM study (GHB - Use and Misuse) is a longitudinal retrospective study that was conducted between 2005 and 2007 in seven centres in Northern Italy [4].
Feb 02 · PIV GATE 1 study to evaluate the efficacy of SMO in comparison to oxazepam in the treatment of alcohol withdrawal symptoms starts (NCT02090504). 127 adults will be recruited in Austria and Italy. The study is due to complete May 09 [3].

Evidence based evaluations