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

NCT ID: NCT02832037

Last Updated: 2021-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 509 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-25
• Study Completion Date: 2020-01-29

Brief 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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BI 425809 dose 1

Group Type: EXPERIMENTAL

BI 425809 dose 1

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 425809 dose 2

Group Type: EXPERIMENTAL

BI 425809 dose 2

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 425809 dose 3

Group Type: EXPERIMENTAL

BI 425809 dose 3

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

BI 425809 dose 4

Group Type: EXPERIMENTAL

BI 425809 dose 4

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

BI 425809 dose 1

Intervention Type: DRUG

BI 425809 dose 2

Intervention Type: DRUG

BI 425809 dose 3

Intervention Type: DRUG

BI 425809 dose 4

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Collaborative Neuroscience Network, LLC (CNS)

Garden Grove, California, United States

Synergy San Diego

Lemon Grove, California, 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

CNRI-San Diego, LLC

San Diego, California, United States

Premier Clinical Research Institute

Miami, Florida, United States

Synexus

Atlanta, Georgia, United States

Atlanta Center

Atlanta, Georgia, United States

Uptown Research Institute

Chicago, Illinois, United States

Lake Charles Clinical Trials LLC

Lake Charles, Louisiana, United States

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, United States

Mid-America Clinical Research, LLC

St Louis, Missouri, United States

University at Buffalo, The State University of New York

Buffalo, New York, United States

Neurobehavioral Research, Inc.

Cedarhurst, New York, United States

Finger Lakes Clinical Research

Rochester, New York, United States

North Carolina Psychiatric Research Center

Raleigh, North Carolina, United States

Midwest Clinical Research

Dayton, Ohio, United States

InSite Clinical Research

DeSoto, Texas, United States

Psychiatric and Behavioral Solutions, LLC

Salt Lake City, Utah, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

Medical University of Innsbruck

Innsbruck, , Austria

AKH - Medical University of Vienna

Vienna, , Austria

Dr. Alexander McIntyre Inc.

Penticton, British Columbia, Canada

The Medical Arts Health Research Group

Vancouver, British Columbia, Canada

Chatham-Kent Clinical Trials Research Centre

Chatham, Ontario, Canada

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, Canada

IUSMM Institut Universitaire en Sante Mentale de Montreal

Montreal, Quebec, Canada

Zentrum für klinische Forschung Dr. med. Irma Schöll & Kollegen

Bad Homburg, , Germany

Praxis Dr. Volker Schumann

Berlin, , Germany

Berufsausübungsgemeinschaft, Dr. sc. med. Alexander Schulze und Prof. Dr. med. Hagen Kunte

Berlin, , Germany

Praxis Dr. Hahn, Berlin

Berlin, , Germany

PANAKEIA Arzneimittelforschung Leipzig GmbH

Leipzig, , Germany

Zentralinstitut für seelische Gesundheit

Mannheim, , Germany

Neurologie und Psychiatrie / Psychotherapie

Westerstede, , Germany

ASST degli Spedali Civili di Brescia

Concesio (BS), , Italy

Asst Santi Paolo E Carlo

Milan, , Italy

Azienda Sanitaria Ospedale S. Luigi Gonzaga

Orbassano (TO), , Italy

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, , Japan

Wlokiennicza Med,Spec.Med.Prac,MD Tomasz Markowski,Bialystok

Bialystok, , Poland

Podlassian Center of Psychogeriatry, 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.

Warsaw, , Poland

Chonnam National University Hospital

Gwangju, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

National Center for Mental Health

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

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, , Spain

NCKUH

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei City Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

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 Kingdom

Countries

United States; Austria; Canada; Germany; Italy; Japan; Poland; South Korea; Spain; Taiwan; United Kingdom

References

Schultheis C, Rosenbrock H, Mack SR, Vinisko R, Schuelert N, Plano A, Sussmuth SD. Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809). Transl Psychiatry. 2022 Aug 11;12(1):329. doi: 10.1038/s41398-022-02096-5.

Reference Type: DERIVED

PMID: 35953474 (View on PubMed)

Fleischhacker WW, Podhorna J, Groschl M, Hake S, Zhao Y, Huang S, Keefe RSE, Desch M, Brenner R, Walling DP, Mantero-Atienza E, Nakagome K, Pollentier S. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry. 2021 Mar;8(3):191-201. doi: 10.1016/S2215-0366(20)30513-7.

Reference Type: DERIVED

PMID: 33610228 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.mystudywindow.com/

Related Info

Other Identifiers

2016-000285-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1346.9

Identifier Type: -

Identifier Source: org_study_id