Psychotic Disorders
Conditions
Brief 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.
Interventions
DRUGBI 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.
DRUGPlacebo
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.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe | Up to 52 weeks. | 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 \[patient-years\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of First Episode of Psychosis | Up to 52 weeks. | 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. |
| Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment | Baseline, week 24 and week 52. | 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. |
| Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment | Baseline and week 52. | 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. |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Baseline and week 52. | 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. |
Countries
Canada, China, United Kingdom, United States
Participant flow
Recruitment details
This was a randomised, placebo-controlled, double-blind, parallel group trial over 52 weeks. The patients were randomised to 1 of the 2 treatment groups at a ratio of 1:1. After completion of the treatment period, or following early discontinuation, patients were to complete a 4-weeks follow-up period.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 24 |
| 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. | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Covid-19 pandemic outbreak | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | non-compliance | 0 | 1 |
| Overall Study | outcome event | 0 | 1 |
| Overall Study | Trial termination | 4 | 5 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | BI 409306 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 23.4 years STANDARD_DEVIATION 4 | 20.9 years STANDARD_DEVIATION 3.8 | 22.1 years STANDARD_DEVIATION 4 |
| Brief Assessment of Cognition (BAC App) composite T score | 52.417 T-score STANDARD_DEVIATION 7.945 | 49.308 T-score STANDARD_DEVIATION 13.451 | 50.800 T-score STANDARD_DEVIATION 11.154 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 24 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Positive and Negative Syndrome Scale (PANSS) Negative scale subtotal | 14.4 Score on a scale STANDARD_DEVIATION 5.1 | 13.4 Score on a scale STANDARD_DEVIATION 3.3 | 13.9 Score on a scale STANDARD_DEVIATION 4.2 |
| Positive and Negative Syndrome Scale (PANSS) Positive scale subtotal | 16.0 Score on a scale STANDARD_DEVIATION 3.9 | 14.5 Score on a scale STANDARD_DEVIATION 3.4 | 15.2 Score on a scale STANDARD_DEVIATION 3.7 |
| Positive and Negative Syndrome Scale (PANSS) total | 62.8 Score on a scale STANDARD_DEVIATION 12.5 | 58.2 Score on a scale STANDARD_DEVIATION 11 | 60.4 Score on a scale STANDARD_DEVIATION 11.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 16 Participants | 21 Participants | 37 Participants |
| Schizophrenia Cognition Rating Scale (SCoRS) total score | 36.333 Score on a scale STANDARD_DEVIATION 7.405 | 36.462 Score on a scale STANDARD_DEVIATION 7.814 | 36.400 Score on a scale STANDARD_DEVIATION 7.543 |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 |
| other Total, other adverse events | 16 / 26 | 21 / 24 |
| serious Total, serious adverse events | 2 / 26 | 1 / 24 |
Outcome results
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 \[patient-years\].
Time frame: Up to 52 weeks.
Population: Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 409306 | Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe | 0.433 remissions per patient-years |
| Placebo | Incidence of Remission From Attenuated Psychosis Syndrome (APS) Within a 52-week Timeframe | 0.446 remissions per patient-years |
p-value: 0.787395% CI: [0.258, 2.795]Regression, Cox
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.
Time frame: Baseline, week 24 and week 52.
Population: All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BI 409306 | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment | Adjusted mean change from baseline at week 24 | -2.12 Score on a scale |
| BI 409306 | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment | Adjusted mean change from baseline at week 52 | -3.05 Score on a scale |
| Placebo | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment | Adjusted mean change from baseline at week 24 | -3.89 Score on a scale |
| Placebo | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 24 and 52 Weeks of Treatment | Adjusted mean change from baseline at week 52 | -6.23 Score on a scale |
Comparison: BI 409306 vs. placebo of change from baseline at week 24. 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.p-value: 0.521295% CI: [-3.773, 7.315]Mixed Models Analysis
Comparison: BI 409306 vs. placebo of change from baseline at week 52. 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.p-value: 0.312795% CI: [-3.071, 9.425]Mixed Models Analysis
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.
Time frame: Baseline and week 52.
Population: All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BI 409306 | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, positive items score | -3.83 Score on a scale |
| BI 409306 | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, negative items score | -0.98 Score on a scale |
| BI 409306 | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, total score | -6.02 Score on a scale |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, positive items score | -3.03 Score on a scale |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, negative items score | -2.41 Score on a scale |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Items Score, Negative Items Score, and Total Score After 52 Weeks of Treatment | Adjusted mean change from baseline at week 52, total score | -7.73 Score on a scale |
Comparison: BI 409306 vs. placebo of change from baseline at week 52, positive items score. 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.p-value: 0.585895% CI: [-3.749, 2.153]Mixed Models Analysis
Comparison: BI 409306 vs. placebo of change from baseline at week 52, negative items score. 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.p-value: 0.344595% CI: [-1.604, 4.462]Mixed Models Analysis
Comparison: BI 409306 vs. placebo of change from baseline at week 52, total score. 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.p-value: 0.715495% CI: [-7.772, 11.196]Mixed Models Analysis
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.
Time frame: Baseline and week 52.
Population: All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) for both timepoints in this endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 409306 | Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment | -1.51 T-score |
| Placebo | Change From Baseline in the Tablet Based Brief Assessment of Cognition (BAC App) Composite T Score After 52 Weeks of Treatment | 3.48 T-score |
Comparison: BI 409306 vs. placebo of change from baseline at week 52. 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.p-value: 0.160295% CI: [-12.033, 2.057]Mixed Models Analysis
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.
Time frame: Up to 52 weeks.
Population: Full Analysis Set (FAS): All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment and who have analysable data (observed or imputed) in at least one efficacy endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 409306 | Incidence of First Episode of Psychosis | 0 first episodes per patient-years |
| Placebo | Incidence of First Episode of Psychosis | 0.125 first episodes per patient-years |