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

Psychotic Disorders Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03230097
• Other study ID #: 1289.32
• Secondary ID: 2016-004973-42
• Status: Terminated
• Phase: Phase 2
• Start date: September 29, 2017
• Est. completion date: April 7, 2021

Study information

• Verified date: June 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: April 7, 2021
• Est. primary completion date: March 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders

Intervention

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
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.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Chatham-Kent Clinical Trials Research Centre	Chatham	Ontario
Canada	University of Alberta Hospital (University of Alberta)	Edmonton	Alberta
Canada	Alan D. Lowe Medicine Professional Corporation	Toronto	Ontario
China	Peking University Sixth Hospital	Beijing
China	Shanghai Mental Health Center	Shanghai
United Kingdom	Holywell Hospital	Antrim
United Kingdom	The Barberry National Centre for Mental Health	Birmingham
United Kingdom	King's College Hospital	London
United Kingdom	University of Manchester	Manchester
United States	Michigan Clinical Research Institute PC	Ann Arbor	Michigan
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Augusta University	Augusta	Georgia
United States	Community Clinical Research, Inc.	Austin	Texas
United States	Boston Medical Center	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Center For Emotional Fitness	Cherry Hill	New Jersey
United States	University of Cincinnati	Cincinnati	Ohio
United States	ProScience Research Group	Culver City	California
United States	PeaceHealth Medical Group	Eugene	Oregon
United States	Precise Research Centers	Flowood	Mississippi
United States	Cherry Health	Grand Rapids	Michigan
United States	University Hills Clinical Research	Irving	Texas
United States	University of Florida College of Medicine	Jacksonville	Florida
United States	Altea Research Institute	Las Vegas	Nevada
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	PRIME Clinic	New Haven	Connecticut
United States	New York State Psychiatric Institute	New York	New York
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Psychiatric and Behavioral Solutions, LLC	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  China,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.

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