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

NCT02832037 | Completed Phase 2 Results

• 2 other identifiers: 1346.92016-000285-28
• Study Type: interventional
• Target: 509
• Locations: 11 countries
• Sites: 81

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment

  Baseline and after 12 weeks of treatment

• 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

Study Arms (5)

BI 425809 dose 1

EXPERIMENTAL

Drug: BI 425809 dose 1; Drug: Placebo

BI 425809 dose 2

EXPERIMENTAL

Drug: BI 425809 dose 2; Drug: Placebo

BI 425809 dose 3

EXPERIMENTAL

Drug: BI 425809 dose 3; Drug: Placebo

BI 425809 dose 4

EXPERIMENTAL

Drug: BI 425809 dose 4; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 425809 dose 1 DRUG

BI 425809 dose 1

BI 425809 dose 2 DRUG

BI 425809 dose 2

BI 425809 dose 3 DRUG

BI 425809 dose 3

BI 425809 dose 4 DRUG

BI 425809 dose 4

Placebo DRUG

BI 425809 dose 1; BI 425809 dose 2; BI 425809 dose 3; BI 425809 dose 4; Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (81)

Collaborative Neuroscience Network, LLC (CNS)

Garden Grove, California, 92845, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Alliance for Wellness

Panorama City, California, 91402, United States

Location

CNRI - Los Angeles

Pico Rivera, California, 90660, United States

Location

CNRI-San Diego, LLC

San Diego, California, 92102, United States

Location

Premier Clinical Research Institute

Miami, Florida, 33122, United States

Location

Synexus

Atlanta, Georgia, 30328, United States

Location

Atlanta Center

Atlanta, Georgia, 30331, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Lake Charles Clinical Trials LLC

Lake Charles, Louisiana, 70629, United States

Location

Michigan Clinical Research Institute PC

Ann Arbor, Michigan, 48105, United States

Location

Mid-America Clinical Research, LLC

St Louis, Missouri, 63109, United States

Location

University at Buffalo, The State University of New York

Buffalo, New York, 14215, United States

Location

Neurobehavioral Research, Inc.

Cedarhurst, New York, 11516, United States

Location

Finger Lakes Clinical Research

Rochester, New York, 14618, United States

Location

North Carolina Psychiatric Research Center

Raleigh, North Carolina, 27610, United States

Location

Midwest Clinical Research

Dayton, Ohio, 45417, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

Psychiatric and Behavioral Solutions, LLC

Salt Lake City, Utah, 84105, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Dr. Alexander McIntyre Inc.

Penticton, British Columbia, V2A 4M4, Canada

Location

The Medical Arts Health Research Group

Vancouver, British Columbia, V7T 1C5, Canada

Location

Chatham-Kent Clinical Trials Research Centre

Chatham, Ontario, N7L 1C1, Canada

Location

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, M5T 1R8, Canada

Location

IUSMM Institut Universitaire en Sante Mentale de Montreal

Montreal, Quebec, H1N 3M5, Canada

Location

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

Bad Homburg, 61348, Germany

Location

Praxis Dr. Volker Schumann

Berlin, 10245, Germany

Location

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

Berlin, 13156, Germany

Location

Praxis Dr. Hahn, Berlin

Berlin, 13187, Germany

Location

PANAKEIA Arzneimittelforschung Leipzig GmbH

Leipzig, 04275, Germany

Location

Zentralinstitut für seelische Gesundheit

Mannheim, 68159, Germany

Location

Neurologie und Psychiatrie / Psychotherapie

Westerstede, 26655, Germany

Location

ASST degli Spedali Civili di Brescia

Concesio (BS), 25062, Italy

Location

Asst Santi Paolo E Carlo

Milan, 20142, Italy

Location

Azienda Sanitaria Ospedale S. Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

Fujita Health University Hospital

Aichi, Toyoake, 470-1192, Japan

Location

Chiba University Hospital

Chiba, Chiba, 260-8677, Japan

Location

National Center for Global Health and Medicine Kohnodai Hospital

Chiba, Ichikawa, 272-8516, Japan

Location

Hospital of the University of Occupational and Environmental Health

Fukuoka, Kitakyushu, 807-8556, Japan

Location

Hokkaido University Hospital

Hokkaido, Sapporo, 060-8648, Japan

Location

Kobe University Hospital

Hyogo, Kobe, 650-0017, Japan

Location

Kagawa University Hospital

Kagawa, Kita-gun, 761-0793, Japan

Location

Kishiro Mental Clinic

Kanagawa, Kawasaki, 214-0014, Japan

Location

Nara Medical University Hospital

Nara, Kashihara, 634-8522, Japan

Location

Kansai Medical University Medical Center

Osaka, Moriguchi, 570-8507, Japan

Location

Iwaki Clinic, Tokushima, Psychosomatic Medicine

Tokushima, Anan, 774-0014, Japan

Location

National Center Neurology and Psychiatry

Tokyo, Kodaira, 187-8851, Japan

Location

Showa University Karasuyama Hospital

Tokyo, Setagaya, 157-8577, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, Shinjuku-ku, 162-8666, Japan

Location

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

Bialystok, 15 464, Poland

Location

Podlassian Center of Psychogeriatry, Bialystok

Bialystok, 15-756, Poland

Location

Osrodek Badan Klinicznych CLINSANTE S.C.

Bydgoszcz, 85794, Poland

Location

Non-public Health Care Psychiatric Institution MENTIS,Leszno

Leszno, 64100, Poland

Location

EUROMEDIS Sp. z o.o., Szczecin

Szczecin, 70-111, Poland

Location

Clin.Research Centre Clinsante SC Ewa Galczak-Nowak,Torun

Torun, 87-100, Poland

Location

Therapy Centre DIALOG Sp.z o.o. S.j.

Warsaw, 02-791, Poland

Location

Chonnam National University Hospital

Gwangju, 61453, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

National Center for Mental Health

Seoul, 04933, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Centro de Salud Mental de Fuencarral

Madrid, 28029, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Puerta de Hierro

Majadahonda (Madrid), 28222, Spain

Location

Centro de Salud de San Juan

Salamanca, 37005, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10016, Taiwan

Location

Taipei City Hospital

Taipei, 110, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Bushey Fields Hospital

Dudley, DY1 2LZ, United Kingdom

Location

Royal Edinburgh Hospital

Edinburgh, EH10 5HF, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

King's College Hospital

London, SE5 8AF, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3HD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35953474 DERIVED

• 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.

  PMID: 33610228 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Limitations and Caveats

After identifying a new major metabolite (BI 761036), the sponsor communicated a voluntary hold of Phase II to relevant competent authorities on 16-Sep-2016. This was formalized to a full clinical hold of the development program by the Food and Drug Administration (FDA) on 26-Oct-2016. Before start of the hold, 1 patient was screened, but not randomized. Clinical hold was removed by FDA on 21-Nov-2017, the trial was re-initiated with version 3 of the clinical trial protocol, dated 13-Dec-2017.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2016
• First Posted: July 13, 2016
• Study Start: July 25, 2016
• Primary Completion: December 27, 2019
• Study Completion: January 29, 2020
• Last Updated: February 24, 2021
• Results First Posted: February 24, 2021

Record last verified: 2021-02

Locations

IT (3); KR (7); CA (5); TW (4); AU (2); PL (7); DE (7); ES (6); GB (5); US (21); JP (14)