Abstract
Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.
| Original language | English |
|---|---|
| Pages (from-to) | 18-30 |
| Number of pages | 13 |
| Journal | European Neuropsychopharmacology |
| Volume | 52 |
| Early online date | 6 Jul 2021 |
| DOIs | |
| Publication status | Published - Nov 2021 |
Bibliographical note
Funding Information:JG is employed by D&A Pharma, Paris, France. RP and QR were employed by D&A Pharma when the data were analysed. None of the other authors received financial support for the current work. GA, HJA, PB, AB, Antoni Gual, OL, IM, PP, BS, HW were investigators for the study. WvdB received financial support related to the current work from Lundbeck, Novartis, Bioproject, and Kinnov Therapeutics. WvdB received financial support not related to the current work from Recordati, Mundipharma, Angelini, Opiant, Indivior, and Takeda. GA and OL served as consultants for D&A Pharma, and were paid for their consulting services. GA has received lecture fees from D&A Pharma. RS received financial compensation from D&A Pharma for consultations. IM served as board member for Angelini, Camurus, CT Sanremo, D&A Pharma, Gilead, Indivior, Lundbeck, Molteni, MSD, Mundipharma. HJA reported being member of advisory boards or DSMB for Bioprojet, CV Sciences, and Ethypharm, and has received sponsorship to attend scientific meetings, speaker honoraria or consultancy fees from Bioprojet, D&A Pharma, Ethypharm, Kinnov Pharmaceuticals and Lundbeck. He is also member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative (ACTIVE), which was supported in the last three years by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. Antoni Gual received funding from Novartis to conduct a trial on cocaine dependence and fees as speaker from Alkohol & Samfund.
Publisher Copyright:
© 2021 The Authors
Keywords
- Alcohol dependence
- Alcohol use disorders
- GHB
- Maintenance of abstinence
- RCT
- Sodium oxybate
