This Study Tests Whether BI 409306 Prevents Patients With a Specific Type of Mental Illness (Attenuated Psychosis Syndrome) From Becoming Worse. This Study Looks at How Well Patients Tolerate the Medicine and How Effective it is Over 1 Year

A Phase II Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered BI 409306 During a 52-week Treatment Period as an Early Intervention in Patients With Attenuated Psychosis Syndrome.

This is a study in people between 16 and 30 years of age who have a specific type of mental illness called attenuated psychosis syndrome (APS). The purpose of this study is to find out whether BI 409306 helps reduce the symptoms of APS.

Participants are in the study for 1 year and 2 months. During this time, they visit the study site about 15 times and get about 10 phone calls. Participants are put into 2 groups by chance. They get either BI 409306 or placebo. Placebo tablets look like BI 409306 tablets but do not contain any medicine. Participants take a BI 409306 or placebo tablet two times a day.

During the study, participants answer questions in interviews and complete questionnaires so the doctors can check whether the APS symptoms change. The doctors also check the general health of the participants.

Study Overview

• Status: Terminated
• Conditions: Psychotic Disorders
• Intervention / Treatment: Drug: BI 409306; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital (University of Alberta)
  • Ontario
    • Chatham, Ontario, Canada, N7L 1C1
      • Chatham-Kent Clinical Trials Research Centre
    • Toronto, Ontario, Canada, L3R 1A3
      • Alan D. Lowe Medicine Professional Corporation
• China
  • Beijing, China, 100089
    • Peking University Sixth Hospital
  • Shanghai, China, 200030
    • Shanghai Mental Health Center
• United Kingdom
  • Antrim, United Kingdom, BT41 2RJ
    • Holywell Hospital
  • Birmingham, United Kingdom, B15 2SJ
    • The Barberry National Centre for Mental Health
  • London, United Kingdom, SE5 8AF
    • King's College Hospital
  • Manchester, United Kingdom, M13 9PL
    • University of Manchester
• United States
  • California
    • Culver City, California, United States, 90230
      • Proscience Research Group
    • San Diego, California, United States, 92103
      • University of California San Diego
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • PRIME Clinic
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute PC
    • Grand Rapids, Michigan, United States, 49503
      • Cherry Health
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
  • Oregon
    • Eugene, Oregon, United States, 97401
      • PeaceHealth Medical Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
    • Irving, Texas, United States, 75062
      • University Hills Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric And Behavioral Solutions, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Meet diagnostic criteria for attenuated psychosis syndrome as defined in DSM-5 and determined by SIPS administered at screening and diagnosis confirmed by NeuroCog Trials after review of video-taped SIPS interview.
• Age ≥16 and ≤ 30 years at the time of consent/assent.

• Male or female patients willing to use highly effective methods of contraception.

  • Female patients of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Patients must agree to use birth control throughout the trial and for at least 28 days after treatment has ended. Acceptable methods of birth control include combined estrogen-progestin oral, intravaginal or transdermal contraceptives, progestogen-only oral, injectable or implantable contraceptives, intrauterine devices (IUDs), intrauterine hormone releasing systems (IUSs), bilateral tubal occlusion, vasectomized sexual partner, and complete sexual abstinence (if acceptable by local health authorities) is allowed when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Male patients who are able to father a child must be ready and able to be abstinent or use adequate contraception for the duration of study participation and for at least 28 days after treatment has ended.
• Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to any study-related procedures OR signed and dated informed consent provided by the patient's parent(s) (or legal guardian) and assent by the patient prior to any study-related procedures in accordance with GCP and local legislation. If the patient has a legal representative, then this legal representative must give written informed consent as well.

Exclusion criteria

• Present or past diagnosis of schizophrenia, schizophreniform, schizoaffective disorder, bipolar disorder I, major depressive disorder with psychotic features, delusional disorder, brief psychotic disorder, other specified schizophrenia spectrum and other psychotic disorder (except attenuated psychosis syndrome), and unspecified schizophrenia spectrum and other psychotic disorder, according to DSM-5.
• Patients taking antipsychotic medication for less than 8 weeks, or patients taking antipsychotic medication for a longer duration but who have not been on a stable dose for 8 weeks prior to informed consent.
• Patients who begin taking an antipsychotic between Visit 1 and Visit 2.
• Patients who have discontinued an antipsychotic medication less than two weeks prior to randomization.
• Patients taking Clozapine.
• Suicidal behavior in the past 2 years reported in the Columbia Suicide Severity Rating Scale (C-SSRS) with a lethality of attempt ≥1, or with a lethality of 0 but a potential lethality of 2, or that in the judgement of the investigator would jeopardize the patient's safety while participating in the trial. The investigator/qualified rater must review all screening C-SSRS reports prior to randomization, documenting an additional interview assessing lethality of the behavior history when appropriate.
• Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent).
• In the judgment of the investigator, any clinically significant finding from the physical examination or laboratory value deviating from normal or any evidence of a clinically significant concomitant disease or any other clinical condition that would jeopardize a patient's safety while participating in the clinical trial.
• Known diseases of the central nervous system (including but not limited to any kind of seizures or stroke).
• History of significant head injury (>5 minutes without consciousness).
• A serious developmental disorder that in the judgement of the investigator would inhibit the patient's ability to comply with all study procedures, or mental retardation (documented IQ <70), or acute attenuated symptoms exclusively related to intoxication from a psychotropic substance.
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
• Planned elective surgery requiring general anesthesia, or hospitalization for more than 1 day during the study period.
• Meets criteria for Substance Use Disorder (DSM-5) within the six months prior to informed consent/assent.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Patients taking strong or moderate CYP1A2 inhibitors who are also a CYP2C19 Poor Metabolizer (PM). Patients taking medication known to be a strong or moderate inhibitor of CYP1A2 must be prospectively genotyped to ensure they are not poor metabolizers of CYP2C19. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the ISF.).
• Patients taking strong or moderate CYP1A2 inhibitors who are also taking concomitant strong or moderate CYP2C19 inhibitors. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the ISF.)
• Patients with a history of moderate to severe hepatic impairment (Child-Pugh B / C).
• Patients with a history of moderate to severe renal impairment (Stage 3 - 5).
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• In the judgment of the investigator, inability of the patient to comply with the clinical trial procedures.
• Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
• Previous participation in any BI 409306 study.
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 409306; Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.	Drug: BI 409306; 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.
Placebo Comparator: Placebo; Patients meeting Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for attenuated psychosis syndrome (APS) per the Structured Interview for Psychosis-Risk Syndromes (SIPS) took placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.	Drug: Placebo; placebo matching 50 milligrams BI 409306, as a film-coated tablet, orally twice a day at approximately the same time every day in the morning and in the evening (approximately 12 hours apart) with or without food for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe	Incidence of remission from attenuated psychosis syndrome (APS) within a 52-week timeframe. The incidence rate per patient-years of remission from attenuated psychosis syndrome (APS) is reported. Remission from APS is defined as a score of <3 on all of the five Positive Symptom items of the Scale of Prodromal Symptoms (SOPS) and maintained until the end of treatment. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms. incidence rate = number of events/total time at risk [patient-years].	Up to 52 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of First Episode of Psychosis	Incidence of first episode of psychosis. The incidence rate per patient-years of psychosis is reported, psychosis is defined as one or more positive Scale of Prodromal Symptoms (SOPS) symptoms rated a 6 AND either a symptom is seriously disorganizing or dangerous OR one of the symptoms above occurred at least one hour per day at an average frequency of four days/week over the past month. OR a new prescription or increase in dose of an ongoing antipsychotic medication. The SOPS provides a 6-point scale (minimum of 0 and maximum of 6, higher score indicating worse symptoms) to quantitatively rate the severity of five attenuated positive symptoms.	Up to 52 weeks.
Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment	Change from baseline (Day -28 to -7) in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) total score after 24 and 52 weeks of treatment. 20-item assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each of the 20 items of the SCoRS is rated on a 4-point scale (minimum of 1 and maximum of 4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (minimum of 20 and maximum of 80). Data analyzed using the restricted maximum likelihood (REML) mixed effects model with repeated measurements (MMRM) including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.	Baseline, week 24 and week 52.
Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment	Change from baseline (Day -28 to -7) in the tablet based Brief Assessment of Cognition (BAC App) composite T score after 52 weeks of treatment. The BAC consists of five tests assessing multiple domains of cognitive function: Verbal Memory, Digit Sequencing, Semantic and Letter Fluency, Symbol Coding, and Tower of London. A composite T score that is calculated using the five standardized scaled sub-test scores was generated (averages five of the standardized scaled sub-test scores, token motor test score not included), larger T-score indicates better cognition. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline North American Prodromal Longitudinal Study (NAPLS) risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction. T-scores in the general population have a mean of 50 and standard deviation of 10.	Baseline and week 52.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment	Change from baseline (Day -28 to -7) in Positive and Negative Syndrome Scale (PANSS) positive items score, negative items score, and total score after 52 weeks of treatment. The PANSS positive and negative symptom scales each have 7 items, and the General Psychopathology Scale (not reported) has 16 items. The patient is rated from 1 to 7 on the 30 different items based on the interview, as well as reports from an informant when possible. Total score is the sum of the score of the 30 items (minimum 30, maximum 210), subtotal are the sum of either the positive or negative scales (minimum 7, maximum 49), lower scores represent an improvement in schizophrenia symptoms. Data analyzed using the REML MMRM including fixed, categorical effects of treatment, visit, treatment by visit interaction, baseline NAPLS risk score, baseline use of antipsychotic medication and continuous fixed covariates of baseline score and baseline-by-visit interaction.	Baseline and week 52.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• Keefe RSE, Woods SW, Cannon TD, Ruhrmann S, Mathalon DH, McGuire P, Rosenbrock H, Daniels K, Cotton D, Roy D, Pollentier S, Sand M. A randomized Phase II trial evaluating efficacy, safety, and tolerability of oral BI 409306 in attenuated psychosis syndrome: Design and rationale. Early Interv Psychiatry. 2021 Oct;15(5):1315-1325. doi: 10.1111/eip.13083. Epub 2020 Dec 22.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2017
• Primary Completion (Actual): March 17, 2021
• Study Completion (Actual): April 7, 2021

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Psychotic Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; BI 409306
• Other Study ID Numbers: 1289.32; 2016-004973-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• IPD Sharing Access Criteria: For study documents - upon signing of a "Document Sharing Agreement". For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No