Effect of gaboxadol on sleep in adult and elderly patients with primary insomnia: Results from two randomized, placebo-controlled, 30-night polysomnography studies

Study Objectives: To evaluate the efficacy and tolerability of gaboxadol in the treatment of adult and elderly patients with primary insomnia. Design: Randomized, double-blind, placebo-controlled, multicenter, 30-night, polysomnography studies. Setting: Sleep laboratory. Patients: Primary insomnia. 18-64 y (adult study), or 65 y (elderly study). Interventions: Adult study: gaboxadol 15 mg (GBX15; N = 148), 10 mg (GBX10: N = 154), or placebo (N = 156); elderly study: GBX1 0 (N 157), gaboxadol 5 mg (GBX5; N = 153), or placebo (N=176). Measurements and Results: Primary endpoints were wake after sleep onset (WASO) and latency to persistent sleep (LPS). Slow wave sleep (SWS) was a secondary endpoint. Analyses were based on the change from baseline for the average of nights 1/2, and nights 29/30, and compared gaboxadol versus placebo. Exploratory endpoints included patient's subjective assessment of total sleep time (sTST), WASO (sWASO), time to sleep onset (sTSO), and number of awakenings (sNAW): these analyses were based on weekly means. 1) Adult study. GBX15 significantly (P <= 0.05) improved WASO through nights 29/30 but had no significant effects on LPS. No significant differences were seen for GBX10 versus placebo on WASO or LPS. GBX15 and GBX10 enhanced SWS. GBX15 significantly improved sTST, sWASO, sTSO, and sNAW at weeks 1 and 4.2) Elderly study. GBX10 significantly improved WASO through nights 29/30; a significant improvement was also seen for GBX5 at nights 1/2 but this was not maintained through nights 29/30. GBX10 significantly improved LPS at nights 112 but the improvement was not maintained through nights 29/30-1 no significant differences were seen for GBX5 versus placebo on LPS. GBX10 and GBX5 enhanced SWS. GBX10 significantly improved sTST at week 1, and sTST, sWASO, and sNAW at week 4. Gaboxadol was generally well tolerated in both studies. Conclusions: The maximum studied doses of gaboxadol (GBX15 in adult patients and GBX10 in elderly patients) were effective at enhancing objective polysomnography measures of sleep maintenance and SWS, and also some subjective sleep measures, over 30 nights but had little or no effects on sleep onset. The clinical relevance of the enhancement of SWS by gaboxadol is unclear.