Cargando…

A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale

AIM: Attenuated psychosis syndrome (APS), a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders‐5, comprises psychotic symptoms that are qualitatively similar to those observed in schizophrenia but are less severe. Patients with APS are at high risk of converting...

Descripción completa

Detalles Bibliográficos
Autores principales: Keefe, Richard S. E., Woods, Scott W., Cannon, Tyrone D., Ruhrmann, Stephan, Mathalon, Daniel H., McGuire, Philip, Rosenbrock, Holger, Daniels, Kristen, Cotton, Daniel, Roy, Dooti, Pollentier, Stephane, Sand, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Publishing Asia Pty Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451588/
https://www.ncbi.nlm.nih.gov/pubmed/33354862
http://dx.doi.org/10.1111/eip.13083
_version_ 1784569878629318656
author Keefe, Richard S. E.
Woods, Scott W.
Cannon, Tyrone D.
Ruhrmann, Stephan
Mathalon, Daniel H.
McGuire, Philip
Rosenbrock, Holger
Daniels, Kristen
Cotton, Daniel
Roy, Dooti
Pollentier, Stephane
Sand, Michael
author_facet Keefe, Richard S. E.
Woods, Scott W.
Cannon, Tyrone D.
Ruhrmann, Stephan
Mathalon, Daniel H.
McGuire, Philip
Rosenbrock, Holger
Daniels, Kristen
Cotton, Daniel
Roy, Dooti
Pollentier, Stephane
Sand, Michael
author_sort Keefe, Richard S. E.
collection PubMed
description AIM: Attenuated psychosis syndrome (APS), a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders‐5, comprises psychotic symptoms that are qualitatively similar to those observed in schizophrenia but are less severe. Patients with APS are at high risk of converting to first‐episode psychosis (FEP). As evidence for effective pharmacological interventions in APS is limited, novel treatments may provide symptomatic relief and delay/prevent psychotic conversion. This trial aims to investigate the efficacy, safety, and tolerability of BI 409306, a potent and selective phosphodiesterase‐9 inhibitor, versus placebo in APS. Novel biomarkers of psychosis are being investigated. METHODS: In this Phase II, multinational, double‐blind, parallel‐group trial, randomized (1:1) patients will receive BI 409306 50 mg or placebo twice daily for 52 weeks. Patients (n = 300) will be enrolled to determine time to remission of APS, time to FEP, change in everyday functional capacity (Schizophrenia Cognition Rating Scale), and change from baseline in Brief Assessment of Cognition composite score and Positive and Negative Syndrome Scale scores. Potential biomarkers of psychosis under investigation include functional measures of brain activity and automated speech analyses. Safety is being assessed throughout. CONCLUSIONS: This trial will determine whether BI 409306 is superior to placebo in achieving sustainable remission of APS and improvements in cognition and functional capacity. These advances may provide evidence‐based treatment options for symptomatic relief in APS. Furthermore, the study will assess the effect of BI 409306 on psychotic conversion and explore the identification of patients at risk for conversion using novel biomarkers.
format Online
Article
Text
id pubmed-8451588
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Wiley Publishing Asia Pty Ltd
record_format MEDLINE/PubMed
spelling pubmed-84515882021-09-27 A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale Keefe, Richard S. E. Woods, Scott W. Cannon, Tyrone D. Ruhrmann, Stephan Mathalon, Daniel H. McGuire, Philip Rosenbrock, Holger Daniels, Kristen Cotton, Daniel Roy, Dooti Pollentier, Stephane Sand, Michael Early Interv Psychiatry Original Articles AIM: Attenuated psychosis syndrome (APS), a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders‐5, comprises psychotic symptoms that are qualitatively similar to those observed in schizophrenia but are less severe. Patients with APS are at high risk of converting to first‐episode psychosis (FEP). As evidence for effective pharmacological interventions in APS is limited, novel treatments may provide symptomatic relief and delay/prevent psychotic conversion. This trial aims to investigate the efficacy, safety, and tolerability of BI 409306, a potent and selective phosphodiesterase‐9 inhibitor, versus placebo in APS. Novel biomarkers of psychosis are being investigated. METHODS: In this Phase II, multinational, double‐blind, parallel‐group trial, randomized (1:1) patients will receive BI 409306 50 mg or placebo twice daily for 52 weeks. Patients (n = 300) will be enrolled to determine time to remission of APS, time to FEP, change in everyday functional capacity (Schizophrenia Cognition Rating Scale), and change from baseline in Brief Assessment of Cognition composite score and Positive and Negative Syndrome Scale scores. Potential biomarkers of psychosis under investigation include functional measures of brain activity and automated speech analyses. Safety is being assessed throughout. CONCLUSIONS: This trial will determine whether BI 409306 is superior to placebo in achieving sustainable remission of APS and improvements in cognition and functional capacity. These advances may provide evidence‐based treatment options for symptomatic relief in APS. Furthermore, the study will assess the effect of BI 409306 on psychotic conversion and explore the identification of patients at risk for conversion using novel biomarkers. Wiley Publishing Asia Pty Ltd 2020-12-22 2021-10 /pmc/articles/PMC8451588/ /pubmed/33354862 http://dx.doi.org/10.1111/eip.13083 Text en © 2020 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Keefe, Richard S. E.
Woods, Scott W.
Cannon, Tyrone D.
Ruhrmann, Stephan
Mathalon, Daniel H.
McGuire, Philip
Rosenbrock, Holger
Daniels, Kristen
Cotton, Daniel
Roy, Dooti
Pollentier, Stephane
Sand, Michael
A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title_full A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title_fullStr A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title_full_unstemmed A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title_short A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale
title_sort randomized phase ii trial evaluating efficacy, safety, and tolerability of oral bi 409306 in attenuated psychosis syndrome: design and rationale
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451588/
https://www.ncbi.nlm.nih.gov/pubmed/33354862
http://dx.doi.org/10.1111/eip.13083
work_keys_str_mv AT keeferichardse arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT woodsscottw arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT cannontyroned arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT ruhrmannstephan arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT mathalondanielh arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT mcguirephilip arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT rosenbrockholger arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT danielskristen arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT cottondaniel arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT roydooti arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT pollentierstephane arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT sandmichael arandomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT keeferichardse randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT woodsscottw randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT cannontyroned randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT ruhrmannstephan randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT mathalondanielh randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT mcguirephilip randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT rosenbrockholger randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT danielskristen randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT cottondaniel randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT roydooti randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT pollentierstephane randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale
AT sandmichael randomizedphaseiitrialevaluatingefficacysafetyandtolerabilityoforalbi409306inattenuatedpsychosissyndromedesignandrationale