A randomised study (D1444C00004) to show superior relapse prevention with quetiapine sustained release (SR) versus placebo.

327 patients with schizophrenia were switched to open-label, once-daily quetiapine SR dosed at 300 mg on Day 1, 600 mg on Day 2, then 400-800 mg for a 16-week stabilisation period. Stable patients (clinically and by dose) were randomised (n=197; double-blind phase) to either quetiapine SR (400-800 mg/day) or placebo. Primary endpoint: time from randomisation to psychiatric relapse (hospitalisation for worsening schizophrenia, PANSS increase ≥30%, CGI-I score ≥6, or need for additional antipsychotics). An independent Data Safety Monitoring Board (DSMB) monitored the study. Planned analyses: interim, after 45 and 60 relapses (to permit termination if a significant treatment difference in primary endpoint was observed); final, after 90 relapses.

Early termination occurred after the first interim analysis (following DSMB recommendation) as quetiapine SR (mean dose 669 mg/day; mean randomised-treatment period 4 months) was significantly superior to placebo for time to relapse: HR 0.16 (95% CI 0.08, 0.34; p<0.001). Numbers (%) of relapses were: 9 (10.7%), quetiapine SR; 36 (41.4%), placebo (interim ITT population). Estimated relapse rate at 6 months was: 14.3%, quetiapine SR; 68.2%, placebo (difference 54% [95% CI 42.5, 65.4; p<0.001]). Incidence of: treatment-related AEs 18% (quetiapine SR), 21% (placebo); total EPS-related AEs 1.1% and 1%, respectively. One patient in each group withdrew due to AEs.

Once-daily quetiapine SR (400-800 mg/day) was effective versus placebo in preventing relapse in patients with clinically-stable schizophrenia and was well tolerated during longer-term use.