Schizophrenia
Conditions
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.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, after 6 and 12 weeks of treatment | MCCB overall composite T-score was derived from scores of 7 cognitive domains (Speed of Processing, Verbal Learning, Working Memory, Reasoning and Problem Solving, Visual Learning, Social Cognition, Attention) obtained from a total of 10 tests (Trail Making, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning, Wechsler Memory Scale, Letter-Number Span, Neuropsychological Assessment Battery, Brief Visuospatial Memory, Category Fluency, Mayer-Salovey-Caruso Emotional Intelligence, Continuous Performance) and ranges typically between -20 and +99, a larger T-score indicates better cognition. Change from baseline in MCCB overall composite T-score after 12 weeks of treatment was modeled using a MMRM with fixed, categorical factors of treatment at each visit, and continuous factors of baseline at each visit, using visit (week 6 and week 12 of treatment) as repeated measures, subject as random effect, adjusted mean (standard error) after 12 weeks of treatment is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | Baseline and after 12 weeks of treatment | SCoRS total score was derived as the sum of non-missing responses from 20 interview-based items rated by an interviewer on a 4-point scale. A response of not available to an item was treated as missing. If six or more of the 20 items were missing for a participant at a visit, then the corresponding SCoRS total score was missing for that participant at the visit. If five or less of the 20 items were missing for a participant at a visit, then the item(s) with missing value(s) were imputed first with the average of the non-missing item values, then the SCoRS total score for the participant at the visit was derived as the sum of non-missing item values and the imputed item values. SCoRS total score is between 20 and 80 where higher score values represent greater degree of impairment in day-to-day functions due to cognitive deficits. Analysis of covariance model was fitted to calculate adjusted mean and standard error, model details in the Statistical Analysis section. |
| Percentage of Participants With Any Adverse Event | 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 | Percentage of participants with any Adverse Event. |
Countries
Austria, Canada, Germany, Italy, Japan, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This was a phase II randomized, double-blind, double-dummy, placebo-controlled, multi-center, multi-national, 12-week parallel-group trial in participants with schizophrenia. Abbreviation: MMRM=Mixed-effects Model Repeated Measures
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 425809 2 mg Once a Day (q.d.) 2 milligram (mg) of BI 425809 administered orally (2 tablets with tablet strength 1 mg BI 425809, 1 placebo tablet matching 25 mg BI 425809 tablets) with water, with or without food, once daily in the morning. Continuous daily dosing for 12 weeks (planned treatment duration). | 85 |
| BI 425809 5 mg q.d. 5 milligram (mg) of BI 425809 administered orally (1 tablet with tablet strength 5 mg BI 425809, 1 placebo tablet matching 1 mg and 5 mg BI 425809 tablets, 1 placebo tablet matching 25 mg BI 425809 tablets) with water, with or without food, once daily in the morning. Continuous daily dosing for 12 weeks (planned treatment duration). | 84 |
| BI 425809 10 mg q.d. 10 milligram (mg) of BI 425809 administered orally (2 tablets with tablet strength 5 mg BI 425809, 1 placebo tablet matching 25 mg BI 425809 tablets) with water, with or without food in the morning, once daily. Continuous daily dosing for 12 weeks (planned treatment duration). | 85 |
| BI 425809 25 mg q.d. 25 milligram (mg) of BI 425809 administered orally (1 tablet with tablet strength 25 mg BI 425809, 2 placebo tablets matching 1 mg and 5 mg BI 425809 tablets) with water, with or without food, once daily in the morning. Continuous daily dosing for 12 weeks (planned treatment duration). | 85 |
| Placebo q.d. Placebo administered orally (2 placebo tablets matching 1 mg and 5 mg BI 425809 tablets, 1 placebo tablet matching 25 mg BI 425809 tablets) with water, with or without food, once daily in the morning. Continuous daily dosing for 12 weeks (planned treatment duration). | 170 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative reasons | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Adverse Event | 5 | 4 | 0 | 2 | 4 |
| Overall Study | Lost to Follow-up | 2 | 0 | 3 | 0 | 5 |
| Overall Study | Protocol Violation | 3 | 0 | 4 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 8 | 0 | 4 | 8 |
Baseline characteristics
| Characteristic | BI 425809 2 mg Once a Day (q.d.) | BI 425809 5 mg q.d. | BI 425809 10 mg q.d. | BI 425809 25 mg q.d. | Placebo q.d. | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.5 years STANDARD_DEVIATION 8.5 | 37.5 years STANDARD_DEVIATION 7.9 | 37.9 years STANDARD_DEVIATION 6.8 | 36.2 years STANDARD_DEVIATION 7.8 | 37.2 years STANDARD_DEVIATION 7.7 | 37.1 years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 7 Participants | 5 Participants | 15 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 76 Participants | 78 Participants | 80 Participants | 155 Participants | 468 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score | 30.0 Score on a scale STANDARD_DEVIATION 13.8 | 32.8 Score on a scale STANDARD_DEVIATION 12 | 31.8 Score on a scale STANDARD_DEVIATION 12.8 | 30.2 Score on a scale STANDARD_DEVIATION 13.2 | 32.3 Score on a scale STANDARD_DEVIATION 13.6 | 31.5 Score on a scale STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 18 Participants | 25 Participants | 22 Participants | 56 Participants | 145 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 20 Participants | 21 Participants | 22 Participants | 41 Participants | 119 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 44 Participants | 39 Participants | 38 Participants | 72 Participants | 237 Participants |
| Sex: Female, Male Female | 34 Participants | 27 Participants | 24 Participants | 35 Participants | 60 Participants | 180 Participants |
| Sex: Female, Male Male | 51 Participants | 57 Participants | 61 Participants | 50 Participants | 110 Participants | 329 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 84 | 0 / 85 | 0 / 85 | 0 / 170 |
| other Total, other adverse events | 22 / 85 | 23 / 84 | 14 / 85 | 13 / 85 | 31 / 170 |
| serious Total, serious adverse events | 2 / 85 | 4 / 84 | 2 / 85 | 4 / 85 | 4 / 170 |
Outcome results
Primary
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
MCCB overall composite T-score was derived from scores of 7 cognitive domains (Speed of Processing, Verbal Learning, Working Memory, Reasoning and Problem Solving, Visual Learning, Social Cognition, Attention) obtained from a total of 10 tests (Trail Making, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning, Wechsler Memory Scale, Letter-Number Span, Neuropsychological Assessment Battery, Brief Visuospatial Memory, Category Fluency, Mayer-Salovey-Caruso Emotional Intelligence, Continuous Performance) and ranges typically between -20 and +99, a larger T-score indicates better cognition. Change from baseline in MCCB overall composite T-score after 12 weeks of treatment was modeled using a MMRM with fixed, categorical factors of treatment at each visit, and continuous factors of baseline at each visit, using visit (week 6 and week 12 of treatment) as repeated measures, subject as random effect, adjusted mean (standard error) after 12 weeks of treatment is reported.
Time frame: Baseline, after 6 and 12 weeks of treatment
Population: The Full Analysis Set included all participants who were randomized and were treated with at least 1 dose of trial medication and who had a non-missing baseline measurement and at least 1 non-missing post-baseline and on-treatment measurement for the primary or secondary efficacy endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 425809 2 mg Once a Day (q.d.) | 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 | 1.784 scores on a scale | Standard Error 0.6805 |
| BI 425809 5 mg q.d. | 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 | 1.641 scores on a scale | Standard Error 0.6656 |
| BI 425809 10 mg q.d. | 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 | 3.486 scores on a scale | Standard Error 0.641 |
| BI 425809 25 mg q.d. | 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 | 3.234 scores on a scale | Standard Error 0.641 |
| Placebo q.d. | 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 | 1.504 scores on a scale | Standard Error 0.4579 |
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0145MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0148MCP-Mod linear in log model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0089MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0038MCP-Mod Sigmoid Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0085MCP-Mod logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.228MCP-Mod beta model fit
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.73395% CI: [-1.332, 1.892]Mixed Models Analysis
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.865595% CI: [-1.45, 1.724]Mixed Models Analysis
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.012295% CI: [0.434, 3.53]Mixed Models Analysis
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.028795% CI: [0.181, 3.28]Mixed Models Analysis
Secondary
Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment
SCoRS total score was derived as the sum of non-missing responses from 20 interview-based items rated by an interviewer on a 4-point scale. A response of not available to an item was treated as missing. If six or more of the 20 items were missing for a participant at a visit, then the corresponding SCoRS total score was missing for that participant at the visit. If five or less of the 20 items were missing for a participant at a visit, then the item(s) with missing value(s) were imputed first with the average of the non-missing item values, then the SCoRS total score for the participant at the visit was derived as the sum of non-missing item values and the imputed item values. SCoRS total score is between 20 and 80 where higher score values represent greater degree of impairment in day-to-day functions due to cognitive deficits. Analysis of covariance model was fitted to calculate adjusted mean and standard error, model details in the Statistical Analysis section.
Time frame: Baseline and after 12 weeks of treatment
Population: The Full Analysis Set included all participants who were randomized and were treated with at least 1 dose of trial medication and who had a non-missing baseline measurement and at least 1 non-missing post-baseline and on-treatment measurement for the primary or secondary efficacy endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 425809 2 mg Once a Day (q.d.) | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | -1.637 units on a scale | Standard Error 0.5992 |
| BI 425809 5 mg q.d. | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | -3.652 units on a scale | Standard Error 0.589 |
| BI 425809 10 mg q.d. | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | -3.078 units on a scale | Standard Error 0.5803 |
| BI 425809 25 mg q.d. | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | -3.887 units on a scale | Standard Error 0.577 |
| Placebo q.d. | Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Total Score After 12 Weeks of Treatment | -2.815 units on a scale | Standard Error 0.4181 |
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.066MCP-Mod linear model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.1619MCP-Mod linear in log model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0832MCP-Mod Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0625MCP-Mod Sigmoid Emax model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.0768MCP-Mod logistic model fit
Comparison: A flat vs. non-flat dose-response relationship across the 4 doses of BI 425809 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 6 different plausible dose-response patterns (linear, linear in log, Emax, Sigmoid Emax, logistic, and beta) while protecting the overall probability of type I error (one-sided alpha of 0.05).p-value: 0.7479MCP-Mod beta model fit
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.1195% CI: [-0.258, 2.613]ANCOVA
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.2595% CI: [-2.257, 0.582]ANCOVA
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.7195% CI: [-1.669, 1.142]ANCOVA
Comparison: Secondary analysis. No formal hypotheses were tested.p-value: 0.1395% CI: [-2.473, 0.328]ANCOVA
Secondary
Percentage of Participants With Any Adverse Event
Percentage of participants with any Adverse Event.
Time frame: 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
Population: The Treated Set included all participants who were randomized and were treated with at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 425809 2 mg Once a Day (q.d.) | Percentage of Participants With Any Adverse Event | 58.8 Percentage of participants |
| BI 425809 5 mg q.d. | Percentage of Participants With Any Adverse Event | 52.4 Percentage of participants |
| BI 425809 10 mg q.d. | Percentage of Participants With Any Adverse Event | 41.2 Percentage of participants |
| BI 425809 25 mg q.d. | Percentage of Participants With Any Adverse Event | 42.4 Percentage of participants |
| Placebo q.d. | Percentage of Participants With Any Adverse Event | 43.5 Percentage of participants |