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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: BI 425809 dose 1; Drug: BI 425809 dose 2; Drug: BI 425809 dose 3; Drug: BI 425809 dose 4

• Study Type: Interventional
• Enrollment (Actual): 509
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medical University of Innsbruck
  • Vienna, Austria, 1090
    • AKH - Medical University of Vienna
• Canada
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 4M4
      • Dr. Alexander McIntyre Inc.
    • Vancouver, British Columbia, Canada, V7T 1C5
      • The Medical Arts Health Research Group
  • Ontario
    • Chatham, Ontario, Canada, N7L 1C1
      • Chatham-Kent Clinical Trials Research Centre
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health (CAMH)
  • Quebec
    • Montreal, Quebec, Canada, H1N 3M5
      • IUSMM Institut Universitaire en Sante Mentale de Montreal
• Germany
  • Bad Homburg, Germany, 61348
    • Zentrum für klinische Forschung Dr. med. Irma Schöll & Kollegen
  • Berlin, Germany, 10245
    • Praxis Dr. Volker Schumann
  • Berlin, Germany, 13156
    • Berufsausübungsgemeinschaft, Dr. sc. med. Alexander Schulze und Prof. Dr. med. Hagen Kunte
  • Berlin, Germany, 13187
    • Praxis Dr. Hahn, Berlin
  • Leipzig, Germany, 04275
    • PANAKEIA Arzneimittelforschung Leipzig GmbH
  • Mannheim, Germany, 68159
    • Zentralinstitut für seelische Gesundheit
  • Westerstede, Germany, 26655
    • Neurologie und Psychiatrie / Psychotherapie
• Italy
  • Concesio (BS), Italy, 25062
    • ASST degli Spedali Civili di Brescia
  • Milano, Italy, 20142
    • ASST Santi Paolo e Carlo
  • Orbassano (TO), Italy, 10043
    • Azienda Sanitaria Ospedale S. Luigi Gonzaga
• Japan
  • Aichi, Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Chiba, Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Chiba, Ichikawa, Japan, 272-8516
    • National Center for Global Health and Medicine Kohnodai Hospital
  • Fukuoka, Kitakyushu, Japan, 807-8556
    • Hospital of the University of Occupational and Environmental Health
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Hyogo, Kobe, Japan, 650-0017
    • Kobe University Hospital
  • Kagawa, Kita-gun, Japan, 761-0793
    • Kagawa University Hospital
  • Kanagawa, Kawasaki, Japan, 214-0014
    • Kishiro Mental Clinic
  • Nara, Kashihara, Japan, 634-8522
    • Nara Medical University Hospital
  • Osaka, Moriguchi, Japan, 570-8507
    • Kansai Medical University Medical Center
  • Tokushima, Anan, Japan, 774-0014
    • Iwaki Clinic, Tokushima, Psychosomatic Medicine
  • Tokyo, Kodaira, Japan, 187-8851
    • National Center Neurology and Psychiatry
  • Tokyo, Setagaya, Japan, 157-8577
    • Showa University Karasuyama Hospital
  • Tokyo, Shinjuku-ku, Japan, 162-8666
    • Tokyo Women's Medical University Hospital
• Korea, Republic of
  • Gwangju, Korea, Republic of, 61453
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seongnam, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 04933
    • National Center for Mental Health
• Poland
  • Bialystok, Poland, 15 464
    • Wlokiennicza Med,Spec.Med.Prac,MD Tomasz Markowski,Bialystok
  • Bialystok, Poland, 15-756
    • Podlassian Center of Psychogeriatry, Bialystok
  • Bydgoszcz, Poland, 85794
    • Osrodek Badan Klinicznych CLINSANTE S.C.
  • Leszno, Poland, 64100
    • Non-public Health Care Psychiatric Institution MENTIS,Leszno
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z o.o., Szczecin
  • Torun, Poland, 87-100
    • Clin.Research Centre Clinsante SC Ewa Galczak-Nowak,Torun
  • Warszawa, Poland, 02-791
    • Therapy Centre DIALOG Sp.z o.o. S.j.
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28029
    • Centro de Salud Mental de Fuencarral
  • Majadahonda (Madrid), Spain, 28222
    • Hospital Puerta de Hierro
  • Salamanca, Spain, 37005
    • Centro de Salud de San Juan
  • Santander, Spain, 39008
    • Hospital Universitario Marques De Valdecilla
• Taiwan
  • Tainan, Taiwan, 704
    • NCKUH
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10016
    • National Taiwan University Hospital
  • Taipei, Taiwan, 110
    • Taipei City Hospital
• United Kingdom
  • Dudley, United Kingdom, DY1 2LZ
    • Bushey Fields Hospital
  • Edinburgh, United Kingdom, EH10 5HF
    • Royal Edinburgh Hospital
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • London, United Kingdom, SE5 8AF
    • King's College Hospital
  • Truro, United Kingdom, TR1 3HD
    • Royal Cornwall Hospital
• United States
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC (CNS)
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Orange, California, United States, 92868
      • NRC Research Institute
    • Panorama City, California, United States, 91402
      • Alliance for Wellness
    • Pico Rivera, California, United States, 90660
      • CNRI - Los Angeles
    • San Diego, California, United States, 92102
      • CNRI-San Diego, LLC
  • Florida
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute PC
  • Missouri
    • Saint Louis, Missouri, United States, 63109
      • Mid-America Clinical Research, LLC
  • New York
    • Buffalo, New York, United States, 14215
      • University at Buffalo, The State University of New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • North Carolina Psychiatric Research Center
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research
  • Texas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric and Behavioral Solutions, LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BI 425809 dose 1	Drug: Placebo; Drug: BI 425809 dose 1
Experimental: BI 425809 dose 2	Drug: Placebo; Drug: BI 425809 dose 2
Experimental: BI 425809 dose 3	Drug: Placebo; Drug: BI 425809 dose 3
Experimental: BI 425809 dose 4	Drug: Placebo; Drug: BI 425809 dose 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2016
• Primary Completion (Actual): December 27, 2019
• Study Completion (Actual): January 29, 2020

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Nootropic Agents; BI 425809
• Other Study ID Numbers: 1346.9; 2016-000285-28 (EudraCT Number)