Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia

Schizophrenia Clinical Trial

Official title:

A Phase II Randomised, Double-blinded, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of 4 Oral Doses of BI 425809 Once Daily Over 12 Week Treatment Period in Patients With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02832037
• Other study ID #: 1346.9
• Secondary ID: 2016-000285-28
• Status: Completed
• Phase: Phase 2
• Start date: July 25, 2016
• Est. completion date: January 29, 2020

Study information

• Verified date: February 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to investigate the efficacy, safety and pharmacokinetics of four different doses of BI 425809 once daily compared to placebo given for 12 weeks in patients with schizophrenia on stable antipsychotic treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 509
• Est. completion date: January 29, 2020
• Est. primary completion date: December 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion criteria:

• Men or women who are 18-50 years (inclusive) of age at time of consent
• Established schizophrenia with the following clinical features:
• Outpatient, with no hospitalization for worsening of schizophrenia within 3 months prior to randomisation
• Medically stable over the prior 4 weeks and psychiatrically stable without symptom exacerbation within 3 months prior to randomisation
• patients who have no more than a moderate severe rating on the Positive and Negative Symptom Scale (PANSS) positive items P1, P3-P7 and no more than a moderate rating on the PANSS positive item P2
• Current antipsychotic and concomitant psychotropic medications as assessed at Visit 1

must meet the criteria below:

• patients may have up to 2 antipsychotics (typical and/or atypical)
• patients must be maintained on current typical and/or atypical antipsychotics other than Clozapine and on current dose for at least 4 weeks prior to randomisation and/or maintained on current long acting injectable antipsychotics and current dose for at least 3 months prior to randomization
• patients must be maintained on current concomitant psychotropic medications, anticholinergics, antiepileptics and/or lithium for at least 3 months prior to randomisation and on current dose for at least 4 weeks prior to randomisation
• Women of child-bearing potential must be ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly.
• Patients must exhibit reliability, physiologic capability, and an educational level sufficient to comply with all protocol procedures, in the investigator´s opinion
• Patients must have an identified informant who will be consistent throughout the study.
• Further inclusion criteria apply

Exclusion criteria:

• Patients who have a categorical diagnosis of another current major psychiatric disorder
• Diseases of the central nervous system that may impact cognitive test performance
• Movement disorder not currently controlled
• Patients receiving another investigational drug or procedure within 30 days or 6 half-lives (whichever is longer) or recent participation in another trial with any cognitive enhancing therapy
• Recent participation in formal cognitive remediation program
• Recent electroconvulsive therapy
• Patients who have been on BI 409306, encenicline or other investigational drug testing effects on cognition in schizophrenia within the last 6 months prior to randomisation or who have previously been on bitopertin
• Participation in a clinical trial with repeated Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments within the last 6 months
• Patients who required change in ongoing stable benzodiazepine or sleep medication regimen within the last 4 weeks prior to randomisation
• Treatment with Clozapine within 6 months prior to randomisation
• Treatment with medical devices (e.g. Transcranial Magnetic Stimulation (TMS), neurofeedback) for any psychiatric condition within the last 3 months prior to randomisation
• Patients taking strong or moderate Cytochrome P450 (CYPA4) inhibitors or inducers within the last 30 days prior to randomization
• Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior) prior to randomisation
• Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent) prior to randomisation
• Known history of Human Immunodeficiency Virus (HIV) infection and/or a positive result for ongoing Hepatitis B or C infection on the Visit 1 central lab report
• Hemoglobin less than 120 g/L (12g/dL) in men or 115 g/L (11.5 g/dL) in women
• History of hemoglobinopathy such as thalassemia major or sickle-cell anemia
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial or men who are able to father a child, unwilling to be abstinent or use adequate contraception for the duration of the study participation and for at least 28 days after treatment has ended
• Significant history of drug abuse disorder (including alcohol) within the last 6 months prior to informed consent or a positive urine drug screen at screening (except for Benzodiazepines taken according to prescription and as an ongoing, stable regimen)
• Further exclusion criteria apply

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• BI 425809 dose 1

• BI 425809 dose 2

• BI 425809 dose 3

• BI 425809 dose 4

• Placebo

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck
Austria	AKH - Medical University of Vienna	Vienna
Canada	Chatham-Kent Clinical Trials Research Centre	Chatham	Ontario
Canada	IUSMM Institut Universitaire en Sante Mentale de Montreal	Montreal	Quebec
Canada	Dr. Alexander McIntyre Inc.	Penticton	British Columbia
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
Canada	The Medical Arts Health Research Group	Vancouver	British Columbia
Germany	Zentrum für klinische Forschung Dr. med. Irma Schöll & Kollegen	Bad Homburg
Germany	Berufsausübungsgemeinschaft, Dr. sc. med. Alexander Schulze und Prof. Dr. med. Hagen Kunte	Berlin
Germany	Praxis Dr. Hahn, Berlin	Berlin
Germany	Praxis Dr. Volker Schumann	Berlin
Germany	PANAKEIA Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Zentralinstitut für seelische Gesundheit	Mannheim
Germany	Neurologie und Psychiatrie / Psychotherapie	Westerstede
Italy	ASST degli Spedali Civili di Brescia	Concesio (BS)
Italy	Asst Santi Paolo E Carlo	Milano
Italy	Azienda Sanitaria Ospedale S. Luigi Gonzaga	Orbassano (TO)
Japan	Fujita Health University Hospital	Aichi, Toyoake
Japan	Chiba University Hospital	Chiba, Chiba
Japan	National Center for Global Health and Medicine Kohnodai Hospital	Chiba, Ichikawa
Japan	Hospital of the University of Occupational and Environmental Health	Fukuoka, Kitakyushu
Japan	Hokkaido University Hospital	Hokkaido, Sapporo
Japan	Kobe University Hospital	Hyogo, Kobe
Japan	Kagawa University Hospital	Kagawa, Kita-gun
Japan	Kishiro Mental Clinic	Kanagawa, Kawasaki
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	Kansai Medical University Medical Center	Osaka, Moriguchi
Japan	Iwaki Clinic, Tokushima, Psychosomatic Medicine	Tokushima, Anan
Japan	National Center Neurology and Psychiatry	Tokyo, Kodaira
Japan	Showa University Karasuyama Hospital	Tokyo, Setagaya
Japan	Tokyo Women's Medical University Hospital	Tokyo, Shinjuku-ku
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	National Center for Mental Health	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Poland	Podlassian Center of Psychogeriatry, Bialystok	Bialystok
Poland	Wlokiennicza Med,Spec.Med.Prac,MD Tomasz Markowski,Bialystok	Bialystok
Poland	Osrodek Badan Klinicznych CLINSANTE S.C.	Bydgoszcz
Poland	Non-public Health Care Psychiatric Institution MENTIS,Leszno	Leszno
Poland	EUROMEDIS Sp. z o.o., Szczecin	Szczecin
Poland	Clin.Research Centre Clinsante SC Ewa Galczak-Nowak,Torun	Torun
Poland	Therapy Centre DIALOG Sp.z o.o. S.j.	Warszawa
Spain	Hospital del Mar	Barcelona
Spain	Centro de Salud Mental de Fuencarral	Madrid
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda (Madrid)
Spain	Centro de Salud de San Juan	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Taiwan	NCKUH	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei City Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Bushey Fields Hospital	Dudley
United Kingdom	Royal Edinburgh Hospital	Edinburgh
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	King's College Hospital	London
United Kingdom	Royal Cornwall Hospital	Truro
United States	Michigan Clinical Research Institute PC	Ann Arbor	Michigan
United States	Atlanta Center	Atlanta	Georgia
United States	Synexus	Atlanta	Georgia
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	University at Buffalo, The State University of New York	Buffalo	New York
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	Uptown Research Institute	Chicago	Illinois
United States	Midwest Clinical Research	Dayton	Ohio
United States	InSite Clinical Research	DeSoto	Texas
United States	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California
United States	Lake Charles Clinical Trials LLC	Lake Charles	Louisiana
United States	Synergy San Diego	Lemon Grove	California
United States	Premier Clinical Research Institute	Miami	Florida
United States	NRC Research Institute	Orange	California
United States	Alliance for Wellness	Panorama City	California
United States	CNRI - Los Angeles	Pico Rivera	California
United States	North Carolina Psychiatric Research Center	Raleigh	North Carolina
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Mid-America Clinical Research, LLC	Saint Louis	Missouri
United States	Psychiatric and Behavioral Solutions, LLC	Salt Lake City	Utah
United States	CNRI-San Diego, LLC	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Cognitive Function as Measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Overall Composite T-score After 12 Weeks of Treatment	MCCB overall composite T-score was derived from scores of 7 cognitive domains (Speed of Processing, Verbal Learning, Working Memory, Reasoning and Problem Solving, Visual Learning, Social Cognition, Attention) obtained from a total of 10 tests (Trail Making, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning, Wechsler Memory Scale, Letter-Number Span, Neuropsychological Assessment Battery, Brief Visuospatial Memory, Category Fluency, Mayer-Salovey-Caruso Emotional Intelligence, Continuous Performance) and ranges typically between -20 and +99, a larger T-score indicates better cognition.; Change from baseline in MCCB overall composite T-score after 12 weeks of treatment was modeled using a MMRM with fixed, categorical factors of treatment at each visit, and continuous factors of baseline at each visit, using visit (week 6 and week 12 of treatment) as repeated measures, subject as random effect, adjusted mean (standard error) after 12 weeks of treatment is reported.	Baseline, after 6 and 12 weeks of treatment
Secondary	Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment	SCoRS total score was derived as the sum of non-missing responses from 20 interview-based items rated by an interviewer on a 4-point scale. A response of "not available" to an item was treated as missing. If six or more of the 20 items were missing for a participant at a visit, then the corresponding SCoRS total score was missing for that participant at the visit. If five or less of the 20 items were missing for a participant at a visit, then the item(s) with missing value(s) were imputed first with the average of the non-missing item values, then the SCoRS total score for the participant at the visit was derived as the sum of non-missing item values and the imputed item values. SCoRS total score is between 20 and 80 where higher score values represent greater degree of impairment in day-to-day functions due to cognitive deficits.; Analysis of covariance model was fitted to calculate adjusted mean and standard error, model details in the Statistical Analysis section.	Baseline and after 12 weeks of treatment
Secondary	Percentage of Participants With Any Adverse Event	Percentage of participants with any Adverse Event.	On-treatment period, that is, from first intake of any trial drug until the last intake of any trial drug (planned: 84 days) + residual effect period (11 days), up to 103 days

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