to a significant dose-by-time interaction (P <0.01). No significant safety issues were noted in any patient taking less than 120 mg/kg. Pharmacokinetic analyses found significant dose-dependent increases in plasma D-serine levels. Furthermore, consistently with prior biomarker studies, lower baseline D-serine levels were significantly correlated with the higher baseline negative symptoms. Peak D-serine at both study initiation and study end correlated with the magnitude of improvement in negative and positive symptoms independently. Composite final Measurement and Treatment Research to Improve Cognition in Schizophrenia score also correlated with peak D-serine levels. These data suggest that 60 mg/kg may be more efficacious than the 30 mg/kg that was used in previous clinical trials with D-serine, and that it maintains the safety profile seen at lower doses. A follow-up double-blind study is ongoing.
