TY - JOUR
T1 - Evaluation of the Efficacy of BI 425809 Pharmacotherapy in Patients with Schizophrenia Receiving Computerized Cognitive Training
T2 - Methodology for a Double-blind, Randomized, Parallel-group Trial
AU - Harvey, Philip D.
AU - Bowie, Christopher R.
AU - McDonald, Sean
AU - Podhorna, Jana
N1 - Funding Information:
The authors would like to thank Songqiao Huang for providing comments on a version of this manuscript. Editorial support in the form of initial preparation of the outline based on input from all authors, and collation and incorporation of author feedback to develop subsequent drafts, assembling tables and figures, copyediting, and referencing was provided by Mark Condon, DPhil, of Fishawack Communications Ltd, UK, and was funded by Boehringer Ingelheim International GmbH.
Funding Information:
PDH has received consulting fees or travel reimbursements from Alkermes, Boehringer Ingelheim, Intra Cellular Therapies, Otsuka America, Roche, Sanofi Pharma, Sunovion Pharma, Takeda Pharma, and Teva Pharma during the past year. He has a research grant from Takeda and from the Stanley Medical Research Foundation. SM is an employee of Boehringer Ingelheim (Canada) Ltd. JP is an employee of Boehringer Ingelheim International GmbH. CRB has received consulting fees from Boehringer Ingelheim, Pfizer, and Lundbeck. He has research funding from Takeda, Lundbeck, and Pfizer, and has received in-kind research user accounts from Scientific Brain Training Pro.
Funding Information:
The work presented here was funded by the trial sponsor, Boehringer Ingelheim International GmbH (study number: 1346-0038, Clinicaltrials.gov identifier: NCT03859973). The sponsor was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Background and Objective: Cognitive impairments associated with schizophrenia (CIAS) predict poor functional outcomes, but there are currently no approved pharmacological treatments for patients with CIAS. Additional cognitive stimulation may be required for pro-cognitive medications to improve efficacy, and computerized cognitive training (CCT) can be used to increase cognitive activity. A trial evaluating the effects of the novel glycine transporter inhibitor BI 425809 compared with placebo, on a background of regularly self-administered CCT in clinically stable patients with schizophrenia has commenced and its methodology is described here. Methods: This Phase II, multinational, randomized, double-blind, placebo-controlled, parallel-group trial will randomize 200 clinically stable outpatients, aged 18–50 years with established schizophrenia and no other major psychiatric disorder, 1:1 to BI 425809 or placebo once daily for 12 weeks. Following screening, which included a 2-week CCT run-in period, patients sufficiently compliant with CCT (target: ≥ 2 h of CCT per week during CCT run-in) will be randomized. During the 12-week treatment period, all patients should complete a total of approximately 30 h of CCT. The primary endpoint is change from baseline in neurocognitive function as measured by the neurocognitive composite score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), after 12 weeks of treatment. Secondary endpoints include change from baseline in overall MCCB score, Schizophrenia Cognition Rating Scale, Positive and Negative Syndrome Scale, and safety (adverse events [AEs]) and serious AEs. Primary and secondary endpoints will be analyzed using the Restricted Maximum Likelihood-based mixed model for repeated measures. Novel endpoints include the Balloon Effort Task to evaluate patients’ motivation and the Virtual Reality Functional Capacity Assessment Tool to assess skills for daily functioning. Discussion: This is one of the largest and longest trials to date to combine pharmacological therapy with CCT in patients with schizophrenia and will determine the benefit of combining BI 425809 pharmacotherapy with cognitive stimulation through self-administered CCT. This trial will further evaluate whether improvements in neurocognition translate into improved everyday functioning, whether self-administered CCT can be effectively implemented in a large multinational trial, and the role of motivation in neurocognitive and functional improvements. Trial Registration: Registered on Clinicaltrials.gov on March 1, 2019 (NCT03859973).
AB - Background and Objective: Cognitive impairments associated with schizophrenia (CIAS) predict poor functional outcomes, but there are currently no approved pharmacological treatments for patients with CIAS. Additional cognitive stimulation may be required for pro-cognitive medications to improve efficacy, and computerized cognitive training (CCT) can be used to increase cognitive activity. A trial evaluating the effects of the novel glycine transporter inhibitor BI 425809 compared with placebo, on a background of regularly self-administered CCT in clinically stable patients with schizophrenia has commenced and its methodology is described here. Methods: This Phase II, multinational, randomized, double-blind, placebo-controlled, parallel-group trial will randomize 200 clinically stable outpatients, aged 18–50 years with established schizophrenia and no other major psychiatric disorder, 1:1 to BI 425809 or placebo once daily for 12 weeks. Following screening, which included a 2-week CCT run-in period, patients sufficiently compliant with CCT (target: ≥ 2 h of CCT per week during CCT run-in) will be randomized. During the 12-week treatment period, all patients should complete a total of approximately 30 h of CCT. The primary endpoint is change from baseline in neurocognitive function as measured by the neurocognitive composite score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), after 12 weeks of treatment. Secondary endpoints include change from baseline in overall MCCB score, Schizophrenia Cognition Rating Scale, Positive and Negative Syndrome Scale, and safety (adverse events [AEs]) and serious AEs. Primary and secondary endpoints will be analyzed using the Restricted Maximum Likelihood-based mixed model for repeated measures. Novel endpoints include the Balloon Effort Task to evaluate patients’ motivation and the Virtual Reality Functional Capacity Assessment Tool to assess skills for daily functioning. Discussion: This is one of the largest and longest trials to date to combine pharmacological therapy with CCT in patients with schizophrenia and will determine the benefit of combining BI 425809 pharmacotherapy with cognitive stimulation through self-administered CCT. This trial will further evaluate whether improvements in neurocognition translate into improved everyday functioning, whether self-administered CCT can be effectively implemented in a large multinational trial, and the role of motivation in neurocognitive and functional improvements. Trial Registration: Registered on Clinicaltrials.gov on March 1, 2019 (NCT03859973).
UR - http://www.scopus.com/inward/record.url?scp=85079225362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079225362&partnerID=8YFLogxK
U2 - 10.1007/s40261-020-00893-8
DO - 10.1007/s40261-020-00893-8
M3 - Article
C2 - 32036587
AN - SCOPUS:85079225362
VL - 40
SP - 377
EP - 385
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
SN - 1173-2563
IS - 4
ER -