Although well-tolerated with no serious adverse events reported, the phosphodiesterase 9 inhibitor BI 409306 did not improve cognitive impairment in schizophrenia, showing comparable results with placebo, according to a study published in Schizophrenia Bulletin.
This multinational (6 countries), multicenter (55 centers), phase II, placebo-controlled, double-blind, parallel-group trial sought to assess the safety, efficacy, and tolerability of BI 409306 10-100 mg in stable patients with schizophrenia, who were receiving antipsychotic treatment. Participants were randomly assigned into a placebo group or into 10, 25, 50, or 100 mg BI 409306 groups, with 516 participants at the start of the trial and 450 by the end of the 12 weeks, which was succeeded by a 4-week follow-up phase.
The 12 active weeks of the study were broken up into 2 stages. During stage 1, changes from baseline scores in the Cambridge Neuropsychological Test Automated Battery were assessed. None of the groups showed efficacy at this point. Stage 2 measured the change from baseline scores in the Measurements and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. There were no significant improvements at this point either and no significant difference between BI 409306 and placebo. Adverse events were reported in 39.5% of participants (n=204), at similar proportions between BI 409306 10 and 25 mg doses and placebo (from 33.3% to 36.5%), and higher proportions with BI 409306 50 mg and 100 mg doses (41.2% and 53.5%). There were 10 serious adverse events reported, all of which were in the placebo group.
Study investigators conclude that although the trial medication was well tolerated, “the primary endpoint of demonstrating efficacy in cognitive function in patients with [cognitive impairment associated with schizophrenia] on stable antipsychotic medications was not met. Based on its favorable safety profile, future clinical trials in differing schizophrenia populations will be of interest.”
This study was supported by Boehringer Ingelheim International GmbH. Please refer to reference for a complete list of authors’ disclosures.
Brown D, Nakagome K, Cordes J, et al. Evaluation of the efficacy, safety, and tolerability of BI 409306, a novel phosphodiesterase 9 inhibitor, in cognitive impairment in schizophrenia: A randomized, double-blind, placebo-controlled, phase II trial [published online May 1, 2018]. Schizophr Bull. doi: 10.1093/schbul/sby049