Clinical trial NCT02832037: Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-07-13
Enrollment: 509
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.
* 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

Primary outcomes:
measure: 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
timeFrame: Baseline, after 6 and 12 weeks of treatment
Secondary outcomes:
measure: Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment
timeFrame: Baseline and after 12 weeks of treatment
measure: Percentage of Participants With Any Adverse Event
timeFrame: 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
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC (CNS)
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Panorama City
country: United States
facility: Alliance for Wellness
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles
state: California
city: San Diego
country: United States
facility: CNRI-San Diego, LLC
state: California
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Atlanta
country: United States
facility: Synexus
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials LLC
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Clinical Research Institute PC
state: Michigan
city: Saint Louis
country: United States
facility: Mid-America Clinical Research, LLC
state: Missouri
city: Buffalo
country: United States
facility: University at Buffalo, The State University of New York
state: New York
city: Cedarhurst
country: United States
facility: Neurobehavioral Research, Inc.
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Raleigh
country: United States
facility: North Carolina Psychiatric Research Center
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research
state: Ohio
city: DeSoto
country: United States
facility: InSite Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Psychiatric and Behavioral Solutions, LLC
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Vienna
country: Austria
facility: AKH - Medical University of Vienna
city: Penticton
country: Canada
facility: Dr. Alexander McIntyre Inc.
state: British Columbia
city: Vancouver
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Chatham
country: Canada
facility: Chatham-Kent Clinical Trials Research Centre
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health (CAMH)
state: Ontario
city: Montreal
country: Canada
facility: IUSMM Institut Universitaire en Sante Mentale de Montreal
state: Quebec
city: Bad Homburg
country: Germany
facility: Zentrum für klinische Forschung Dr. med. Irma Schöll & Kollegen
city: Berlin
country: Germany
facility: Praxis Dr. Volker Schumann
city: Berlin
country: Germany
facility: Berufsausübungsgemeinschaft, Dr. sc. med. Alexander Schulze und Prof. Dr. med. Hagen Kunte
city: Berlin
country: Germany
facility: Praxis Dr. Hahn, Berlin
city: Leipzig
country: Germany
facility: PANAKEIA Arzneimittelforschung Leipzig GmbH
city: Mannheim
country: Germany
facility: Zentralinstitut für seelische Gesundheit
city: Westerstede
country: Germany
facility: Neurologie und Psychiatrie / Psychotherapie
city: Concesio (BS)
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: Asst Santi Paolo E Carlo
city: Orbassano (TO)
country: Italy
facility: Azienda Sanitaria Ospedale S. Luigi Gonzaga
city: Aichi, Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Chiba, Chiba
country: Japan
facility: Chiba University Hospital
city: Chiba, Ichikawa
country: Japan
facility: National Center for Global Health and Medicine Kohnodai Hospital
city: Fukuoka, Kitakyushu
country: Japan
facility: Hospital of the University of Occupational and Environmental Health
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Hyogo, Kobe
country: Japan
facility: Kobe University Hospital
city: Kagawa, Kita-gun
country: Japan
facility: Kagawa University Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: Kishiro Mental Clinic
city: Nara, Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Osaka, Moriguchi
country: Japan
facility: Kansai Medical University Medical Center
city: Tokushima, Anan
country: Japan
facility: Iwaki Clinic, Tokushima, Psychosomatic Medicine
city: Tokyo, Kodaira
country: Japan
facility: National Center Neurology and Psychiatry
city: Tokyo, Setagaya
country: Japan
facility: Showa University Karasuyama Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: National Center for Mental Health
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Bialystok
country: Poland
facility: Wlokiennicza Med,Spec.Med.Prac,MD Tomasz Markowski,Bialystok
city: Bialystok
country: Poland
facility: Podlassian Center of Psychogeriatry, Bialystok
city: Bydgoszcz
country: Poland
facility: Osrodek Badan Klinicznych CLINSANTE S.C.
city: Leszno
country: Poland
facility: Non-public Health Care Psychiatric Institution MENTIS,Leszno
city: Szczecin
country: Poland
facility: EUROMEDIS Sp. z o.o., Szczecin
city: Torun
country: Poland
facility: Clin.Research Centre Clinsante SC Ewa Galczak-Nowak,Torun
city: Warszawa
country: Poland
facility: Therapy Centre DIALOG Sp.z o.o. S.j.
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Centro de Salud Mental de Fuencarral
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Majadahonda (Madrid)
country: Spain
facility: Hospital Puerta de Hierro
city: Salamanca
country: Spain
facility: Centro de Salud de San Juan
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei City Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Dudley
country: United Kingdom
facility: Bushey Fields Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Edinburgh Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.