A 2-week efficacy and safety study of gaboxadol and zolpidem using electronic diaries in primary insomnia outpatients.
OBJECTIVE
To evaluate the efficacy and safety profile of gaboxadol, a selective extrasynaptic GABA(A) agonist (SEGA) previously in development for the treatment of insomnia.


METHODS
This was a randomised, double-blind, placebo-controlled, parallel-group, 2-week, Phase III study of gaboxadol 5, 10 and 15mg in outpatients meeting the DSM-IV criteria of primary insomnia (N=742). Zolpidem 10mg was used as active reference.


RESULTS
At weeks 1 and 2, significant improvement in total sleep time (sTST) compared to placebo was seen for all doses of gaboxadol (all p<0.05). In addition, gaboxadol 10 and 15mg decreased the number of awakenings (sNAW) (p<0.05) while only gaboxadol 15mg improved wakefulness after sleep onset (sWASO) (p<0.05). At week 1, all doses of gaboxadol significantly improved time-to-sleep onset (sTSO) (p<0.05). At week 2, a sustained effect on sTSO was observed for gaboxadol 15mg. Zolpidem also showed effect on all of these variables. Gaboxadol and zolpidem improved sleep quality, freshness after sleep, daytime function and energy at both weeks. Transient rebound insomnia was observed following discontinuation of treatment with zolpidem, but not gaboxadol.


CONCLUSIONS
Gaboxadol 15mg treatment for 2 weeks significantly improved sleep onset and maintenance variables as well as sleep quality and daytime function, as did zolpidem. Gaboxadol 5 and 10mg also showed benefits on most efficacy variables. Gaboxadol was generally safe and well tolerated, with no evidence of withdrawal symptoms or rebound insomnia after discontinuation of short-term treatment. For zolpidem, transient rebound insomnia was observed.
University of Regensburg, Regensburg, Germany.
Göran
G
Hajak
Jan
J
Hedner
Mirjam
M
Eglin
Henrik
H
Loft
Signe I
SI
Stórustovu
Simone
S
Lütolf
Jonas
J
Lundahl
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D001330:Electronic Data Processing; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D016037:Single-Blind Method; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000077334:Zolpidem
D018755:GABA Agonists; D007555:Isoxazoles; D011725:Pyridines; D000077334:Zolpidem; C015542:gaboxadol