Recently, however, a novel glycine transport inhibitor, RG1678, showed significant improvement in negative symptoms as an adjunctive treatment [27,28▪▪] in a large phase II study. This represents the first positive phase II data for an NMDA-based treatment. As results have been primarily published as an abstract for the American College of Neuropsychopharmacology annual meeting [27], limited information is publicly available. Three doses of RG1678 were tested, with efficacy clearly better for the lower doses (10–30 mg) as opposed to 60 mg. Three hundred and twenty-three patients were randomized, and the intent-to-treat (ITT) population included 312 patients and the ‘per protocol’ population (patients who completed 8 weeks of treatment without any major protocol violations) included 231 patients. Negative symptoms showed a significantly greater decrease from baseline in the 10–30 mg dose groups (P <0.05) as compared with placebo in the per protocol group, although negative symptom reductions in the ITT population approached significance in both dose groups (P <0.09). The percentage of responders in the per protocol population was significantly higher in the 10 mg dose group than in the placebo group (65 vs. 43%; P = 0.013). These promising results are being followed up in phase III studies.
