Short-term treatment with gaboxadol improves sleep maintenance and enhances slow wave sleep in adult patients with primary insomnia.
BACKGROUND
Gaboxadol is a selective extrasynaptic GABA(A) agonist, previously in development for the treatment of insomniac patients.


OBJECTIVE
To evaluate the acute efficacy and safety of gaboxadol in primary insomnia (PI).


METHODS
This was a randomised, double-blind, four-way crossover, polysomnograph study comparing gaboxadol 10 and 20 mg (GBX20) to placebo in 40 adults with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for PI. Zolpidem 10 mg was used as an active reference. Treatment was administered on two consecutive nights in each treatment session. Next-day residual effects were evaluated 2 and 9 h after lights on.


RESULTS
Efficacy analysis included the per-protocol population (n = 38) from night 2. GBX20 reduced wake after sleep onset (p < 0.01). Both doses of gaboxadol, but not zolpidem, reduced the number of night awakenings (p < 0.001). GBX20 and zolpidem increased total sleep time (p < 0.05). Neither dose of gaboxadol nor zolpidem significantly reduced sleep onset latency, although a trend was seen for zolpidem. Gaboxadol enhanced slow wave sleep (SWS) dose-dependently (gaboxadol 10 mg: p < 0.01, GBX20: p < 0.001). Patients reported improved sleep quality following GBX20 (p < 0.05). Both doses of gaboxadol were generally well tolerated with almost exclusively mild to moderately severe adverse events (AEs). More frequent and severe AEs followed GBX20. No serious AEs were reported. No drug treatment was associated with next-day residual effects.


CONCLUSIONS
Acute administration of gaboxadol improves sleep maintenance and enhances SWS in a dose-dependent manner in adult patients with PI. Gaboxadol was not associated with next-day residual effects. Gaboxadol was generally well tolerated, although gaboxadol showed a dose-dependent increase in incidence and severity of AEs.
Lundahl
J
J
Department of Neurology, H Lundbeck A/S, International Clinical Research, Ottiliavej 7-9, 2500, Valby, Denmark. jol@lundbeck.com
Staner
L
L
Staner
C
C
Loft
H
H
Deacon
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000379:methods; D018755:GABA Agonists / Q000009:adverse effects / Q000627:therapeutic use; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017286:Polysomnography / Q000379:methods; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D012737:Sex Factors; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D000077334:Zolpidem
D018755:GABA Agonists; D007555:Isoxazoles; D011725:Pyridines; D000077334:Zolpidem; C015542:gaboxadol