1289.32

Boehringer Ingelheim

Binger Strasse 173, Ingelheim am Rhein, Germany, 55216

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

No

No

No

Final

29 Jun 2021

Yes

17 Mar 2021

Yes

07 Apr 2021

Yes

The objective of this study was to investigate the efficacy, safety, and tolerability of BI 409306 compared with placebo given for 52 weeks to patients with attenuated psychosis syndrome (APS). The study was designed to show superiority of BI 409306 over placebo in achieving remission from APS, as well as improvement in cognition and functional capacity.

Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.

17 Oct 2017

No

Yes

United States: 45

China: 1

Canada: 4

50

0

0

0

0

0

0

5

45

0

0

Overall Study (overall period)

Randomised - controlled

Yes

BI 409306

Film-coated tablet

Oral use

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

Film-coated tablet

Oral use

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.

BI 409306

Placebo

BI 409306

Placebo

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. 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.

Primary

Up to 52 weeks

Stratified (by baseline use of antipsychotic medication) Cox proportional hazards model was used. Treatment effect and NAPLS risk score as covariates.

BI 409306 v Placebo

50

Pre-specified

0.849

2-sided

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. 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.

Secondary

Up to 52 weeks.

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. Each of the 20 items of the SCoRS is rated on a 4-point scale (range: 1-4). Higher ratings reflect a greater degree of impairment. The composite score will be the sum of the 20 items (range: 20-80). 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. 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 for both timepoints.

Secondary

Baseline, week 24 and week 52.

BI 409306 vs. placebo of change from baseline at week 24.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.

BI 409306 v Placebo

25

Pre-specified

1.77

2-sided

BI 409306 vs. placebo of change from baseline at week 52. 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.

BI 409306 v Placebo

25

Pre-specified

3.18

2-sided

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 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.All patients who 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.

Secondary

Baseline and week 52.

BI 409306 vs. placebo of change from baseline at week 52. 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.

BI 409306 v Placebo

16

Pre-specified

-4.99

2-sided

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. 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.

Secondary

Baseline and week 52.

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.

BI 409306 v Placebo

19

Pre-specified

-0.8

2-sided

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.

BI 409306 v Placebo

19

Pre-specified

1.71

2-sided

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.

BI 409306 v Placebo

19

Pre-specified

1.43

2-sided

From treatment start date until the date of discontinuation of trial medication + 7 days, up to 381 days.

The treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

24.0

Placebo

BI 409306