F17464 is a new highly potent preferential D3 antagonist, 5-HT1A and weak D2 partial agonist, with confirmed antipsychotic-like activity in animal models. In healthy volunteers, F17464 had a good safety and tolerability profile. A PET-scan study determined a high D3 occupancy rate up to 22 h after a single dose.

The primary objective was to evaluate the efficacy of 40 mg/day of oral F17464 in comparison to placebo.

This double-blind, parallel group, multicenter study included patients with acute exacerbation of schizophrenia treated for 6 weeks as antipsychotic monotherapy. Patients were hospitalised for the first 3 weeks of treatment, then continued as outpatients.

The 144 randomized patients had a baseline PANSS mean (SD) total score was 89.6 (9.5). The change from baseline of PANSS total score to Day 43 on the FAS (LOCF), showed a statistically significant difference in favor of F17464 over placebo: adjusted mean (SE) change −13.5 (2.1) on F17464 and −7.8 (2.2) on placebo with a treatment effect estimate −5.7 (2.7). The 20% or 30% response rate was statistically higher in the F17464 group (47.2% and 25.0%) compared to the placebo group (30.6% and 13.9%). The incidence of treatment-emergent adverse events was slightly higher in the F17464 group (70.8%) than in the placebo group (62.5%). There were no clinically-relevant hepatic, metabolic, or cardiovascular abnormalities. No EPS was reported under F17464.

This is the first D3 antagonist that proves efficacy. The results of this phase 2 study also demonstrate the favorable safety profile of F17674 when compared to placebo.

The authors have not supplied their declaration of competing interest.