@article{ref1,
title="A Phase IC Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Cognitive Outcomes of BI 409306 in Patients with Mild-to-Moderate Schizophrenia",
journal="Neurology and therapy",
year="2018",
author="Brown, D. and Daniels, K. and Pichereau, S. and Sand, M.",
volume="7",
number="1",
pages="129-139",
abstract="INTRODUCTION: This randomized, double-blind, parallel-group study investigated the safety, tolerability, pharmacokinetics (PK), and cognitive outcomes of BI 409306--a selective phosphodiesterase 9A (PDE9A) inhibitor--in patients with schizophrenia. <br><br>METHODS: Patients with mild-to-moderate schizophrenia were randomized (1:1:1:1) to receive BI 409306 at 25, 50, or 100 mg or placebo once daily over 14 days. The primary endpoints were safety and tolerability; the secondary endpoints were PK and cognitive outcomes. <br><br>RESULTS: Of the 40 randomized patients, 38 (95%) completed the study. Patients were predominantly male (87.5%; mean age, 40.2 years). After a single dose, Cmax was reached within 30-45 min. The geometric mean (gMean) Cmax and AUC0-∞ ranged from 138 to 998 nmol/L and 217 to 2020 nmol∙h/L, respectively. Elimination was rapid (gMean t1/2 range 1.10-1.85 h). After multiple doses, Cmax,ss was reached within 1 h; elimination was similar to that observed after a single dose. Total exposure at steady state and after a single dose were similar (accumulation ratio range: AUC, 0.758-1.13 and Cmax, 0.768-1.40). No deaths, adverse events (AEs) leading to discontinuation, or serious AEs were observed. Treatment-emergent AEs were mild, with no apparent dose-related trends. There was no worsening of schizophrenia symptoms (Positive and Negative Syndrome Scale) and no trends in suicidality (Columbia Suicide Severity Rating Scale). The Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) showed no effect on cognitive function. <br><br>CONCLUSION: Administration of BI 409306 in patients with mild-to-moderate schizophrenia resulted in satisfactory safety and tolerability. BI 409306, PK was characterized by rapid absorption, monophasic to biphasic elimination, and minor accumulation with multiple dosing. Trial Registration: ClinicalTrials.gov identifier NCT01892384. Funding: Boehringer Ingelheim Pharma GmbH &amp; Co. KG. © 2017, The Author(s).<p /><p>Language: en</p>",
language="en",
issn="2193-8253",
doi="10.1007/s40120-017-0085-5",
url="http://dx.doi.org/10.1007/s40120-017-0085-5"
}