Introduction: Treatment resistance constitutes the highest burden of disease within schizophrenia. We hypothesized that the synergistic activity of Lu AF35700 at dopamine D<sub>1</sub> and D<sub>2</sub> receptors might provide superior antipsychotic effects versus first-line antipsychotic therapy in patients with treatment resistant schizophrenia (TRS), with a benign tolerability profile.
Methods: This was a randomized, double-blind, active-controlled clinical trial (NCT02717195) followed by a one year open-label safety extension (NCT02892422). Following prospective confirmation of treatment resistance, patients were randomized (1:1:1) to 10 weeks double-blind treatment with Lu AF35700 10 mg or 20 mg, or active comparator (risperidone or olanzapine).
Results: 1628 patients were screened for TRS, of which 1092 entered the prospective confirmation period. Of these, 697 were randomized (Lu AF35700 10 mg n = 235, 20 mg n = 232, comparator n = 230) and 395 discontinued before randomization, including 264 (24 %) who responded to treatment. 586 patients completed the double-blind phase, of which 524 entered the open-label extension and 318 completed 1-year of open-label treatment. At the end of the double-blind phase, the mean ± SE change in positive and negative syndrome scale (PANSS) total score was -10.1 ± 0.96 for Lu AF35700 10 mg, -8.22 ± 0.98 for Lu AF35700 20 mg, and - 9.90 ± 0.97 for the comparator group. Treatment differences [95 % CI] versus comparator treatment were non-significant (-0.12 [-2.37; 2.13] and 1.67 [-0.59; 3.94], respectively). The most common adverse events with Lu AF35700 were increased weight and headache. Prolactin values decreased by ≥50 % in both sexes treated with Lu AF35700.
Conclusions: Despite evidence of antipsychotic efficacy, treatment with Lu AF35700 failed to differentiate from conventional antipsychotic treatment for patients with TRS.
Keywords: Clinical trial; Lu AF35700; Treatment resistant schizophrenia.
Copyright © 2022. Published by Elsevier B.V.