Solid Tumors, KRAS Mutation
Conditions
Brief summary
This study is open to Japanese adults with different types of advanced cancer that are positive for NRAS/KRAS mutations. This is a study in people for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find the highest dose of BI 3011441 that Japanese people with advanced cancer can tolerate. BI 3011441 is a medicine that may turn off a signal by NRAS/KRAS that makes tumours grow. Participants take BI 3011441 as capsules once a day. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors collect information on any health problems of the participants.
Interventions
DRUGBI 3011441
BI 3011441
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be at least 20 years of age at screening. * Signed and dated written informed consent in accordance with Good Clinical Practice(GCP) and local legislation prior to admission to the trial. * Pathologically documented, locally-advanced or metastatic malignancy with previously identified activating Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) or Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation based on local test. * Provision of archival tumor tissue, if available, to confirm retrospectively NRAS or KRAS mutation status and for biomarker assessment. * Willingness to undergo pre- and on-treatment tumour biopsies for pharmacodynamics and biomarker assessment. Patients can be enrolled without tumour biopsy upon agreement between the Investigator and the Sponsor if tumour biopsy is not feasible (Apply only to study site which agreed to conduct biopsy). * Must have either progressed despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage * Must have at least one target lesion that can be measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 * Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Further inclusion criteria apply.
Exclusion criteria
* Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal treatment or anticancer immunotherapy within 2 weeks of the first administration of trial drugs. * Radiotherapy within 4 weeks prior to first administration of BI 3011441 except as follows * Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to start of treatment * Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to start of treatment may be allowed but must be discussed with the sponsor. * Major surgery within 4 weeks prior to start of treatment or scheduled during the projected course of the trial * Previous treatment with a Rat sarcoma (RAS), Mitogen-activated protein kinase (MAPK) targeting agent * Previous treatment with any investigational agent(s) or targeted treatment within 4 weeks (28 days) prior to start of trial drug or concurrent participation in another clinical trial with an investigational device or drug. * Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the study medications * Patients who have a history or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment or central serous retinopathy; for example, predisposing factors of RVO or central serous retinopathy include uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes. * Patients who have visible retinal pathology that is considered a risk factor for RVO or central serous retinopathy as assessed by ophthalmic examination, such as: * Evidence of new optic disc cupping * Evidence of new visual field defects * Intraocular pressure \>21 mm Hg History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥2, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator; Myocardial infarction within 6 months prior to start of treatment. Uncontrolled hypertension is defined as: Blood pressure (BP) measured in a rested and relaxed condition, where systolic BP \>=140 mmHg, or diastolic BP \>= 90 mmHg, with or without medication. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With DLTs in the MTD Evaluation Period | First treatment cycle, the first 28 days following the start of trial medication. | Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding |
| Maximum Tolerated Dose (MTD) of BI 3011441 Monotherapy | First treatment cycle, the first 28 days following the start of trial medication. | Maximum tolerated dose (MTD) of BI 3011441 monotherapy. The MTD was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 0.33 (EWOC criterion) during the MTD evaluation period. The analysis of the MTD was based on a Bayesian 2-parameter logistic regression model (BLRM) with overdose control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With DLTs During the Entire On-treatment Period | From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. | Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding |
| Number of Patients With Grade ≥3 Treatment-related Adverse Events | From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. | Number of participants with Grade ≥3 treatment-related adverse events is reported. The severity of AEs were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The CTCAE grades are Grade 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). |
| Number of Patients With Treatment Related Adverse Events | From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. | Number of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history. |
| Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2. | Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. |
| Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss) | Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16. | Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point at steady state (AUC0-tz,ss) is reported. |
| Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax) | Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2. | Maximum measured concentration of BI 3011441 in plasma (Cmax) is reported. |
| Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss) | Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16. | Maximum measured concentration of BI 3011441 in plasma at steady state (Cmax,ss) is reported. PK samples were collected at the following timepoints. |
Countries
Japan
Participant flow
Recruitment details
This study was a phase 1, open-label trial of BI 3011441 monotherapy dose escalation of Maximum tolerated dose (MTD) determination in Japanese patients with Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS)/Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation positive advanced for whom previous treatment was not successful or no standard treatment exists, unresectable or metastatic refractory solid tumours.
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 |
|---|---|
| 4 mg BI 3011441 The patients were administered 4 milligram (mg) BI 3011441 soft capsule once daily during 4 weeks with water limited to a maximum of 100 milliliters (mL) per capsules, taken without food, at least 1 hour before a meal or 1 hour after a meal. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 3 |
| 6 mg BI 3011441 The patients were administered 6 milligram (mg) BI 3011441 soft capsule once daily during 4 weeks with water limited to a maximum of 100 milliliters (mL) per capsules, taken without food, at least 1 hour before a meal or 1 hour after a meal. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 4 |
| 8 mg BI 3011441 The patients were administered 8 milligram (mg) BI 3011441 soft capsule once daily during 4 weeks with water limited to a maximum of 100 milliliters (mL) per capsules, taken without food, at least 1 hour before a meal or 1 hour after a meal. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first. | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Clinical disease progression | 0 | 1 | 2 |
| Overall Study | Objective disease progression | 3 | 2 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 4 mg BI 3011441 | 6 mg BI 3011441 | 8 mg BI 3011441 | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 13.9 | 55.5 Years STANDARD_DEVIATION 13.3 | 49.5 Years STANDARD_DEVIATION 13.8 | 53.2 Years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 4 | 0 / 8 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 8 / 8 |
| serious Total, serious adverse events | 1 / 3 | 4 / 4 | 6 / 8 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of BI 3011441 Monotherapy
Maximum tolerated dose (MTD) of BI 3011441 monotherapy. The MTD was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal or above 0.33 (EWOC criterion) during the MTD evaluation period. The analysis of the MTD was based on a Bayesian 2-parameter logistic regression model (BLRM) with overdose control.
Time frame: First treatment cycle, the first 28 days following the start of trial medication.
Population: Maximum tolerated dose (MTD) evaluation set: Included all patients from the treated set who were not replaced and were evaluable for the MTD evaluation. Only evaluable for DLTs patients were considered in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 4 mg BI 3011441 | Maximum Tolerated Dose (MTD) of BI 3011441 Monotherapy | NA milligram (mg) |
Primary
Number of Patients With DLTs in the MTD Evaluation Period
Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding
Time frame: First treatment cycle, the first 28 days following the start of trial medication.
Population: Maximum tolerated dose (MTD) evaluation set: Included all patients from the treated set who were not replaced and were evaluable for the MTD evaluation. Only patients with evaluable DLTs are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg BI 3011441 | Number of Patients With DLTs in the MTD Evaluation Period | 0 Participants |
| 6 mg BI 3011441Edit | Number of Patients With DLTs in the MTD Evaluation Period | 0 Participants |
| 8 mg BI 3011441 | Number of Patients With DLTs in the MTD Evaluation Period | 2 Participants |
Comparison: Probability of true DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Comparison: Probability of true DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Comparison: Probability of true DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Secondary
Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss)
Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point at steady state (AUC0-tz,ss) is reported.
Time frame: Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16.
Population: Pharmacokinetic parameter analysis set (PKS): Includes all subjects in the treated set who provided at least one evaluable observation for at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 mg BI 3011441 | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss) | 505 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 8.89 |
| 6 mg BI 3011441Edit | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss) | 973 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 22.9 |
| 8 mg BI 3011441 | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point at Steady State (AUC0-tz,ss) | 833 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 54.7 |
Secondary
Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 3011441 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Time frame: Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2.
Population: Pharmacokinetic parameter analysis set (PKS): Includes all subjects in the treated set who provided at least one evaluable observation for at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 mg BI 3011441 | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 246 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 28.2 |
| 6 mg BI 3011441Edit | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 471 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 35.3 |
| 8 mg BI 3011441 | Area Under the Concentration-time Curve of BI 3011441 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 704 hour * nanomol/ milliliter (h*nmol/mL) | Geometric Coefficient of Variation 39.6 |
Secondary
Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax)
Maximum measured concentration of BI 3011441 in plasma (Cmax) is reported.
Time frame: Cycle 1: Day 1: Within 5 minutes (min) before and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 2 : Within 5 minutes (min) before dosing on Day 2.
Population: Pharmacokinetic parameter analysis set (PKS): Includes all subjects in the treated set who provided at least one evaluable observation for at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 mg BI 3011441 | Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax) | 72.3 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 11.8 |
| 6 mg BI 3011441Edit | Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax) | 91.8 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 27.1 |
| 8 mg BI 3011441 | Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax) | 133 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 32.6 |
Secondary
Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss)
Maximum measured concentration of BI 3011441 in plasma at steady state (Cmax,ss) is reported. PK samples were collected at the following timepoints.
Time frame: Cycle 1: Day 15: Within 5 minutes (min) before drug administration on Day 15, and 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h and optionally 12h. and Day 16 : Within 5 minutes (min) before dosing on Day 16.
Population: Pharmacokinetic parameter analysis set (PKS): Includes all subjects in the treated set who provided at least one evaluable observation for at least one PK endpoint and were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 4 mg BI 3011441 | Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss) | 73.5 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 12.1 |
| 6 mg BI 3011441Edit | Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss) | 124 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 37.2 |
| 8 mg BI 3011441 | Maximum Measured Concentration of BI 3011441 in Plasma at Steady State (Cmax,ss) | 130 nanomol/ liter (nmol/L) | Geometric Coefficient of Variation 54.9 |
Secondary
Number of Patients With DLTs During the Entire On-treatment Period
Number of participants with Dose limiting toxicities (DLT) occurring during the first treatment cycle (first 4 weeks). DLT was defined as any of the following adverse events related to the treatment: * Haematologic toxicities: * Neutropenia Grade 4 lasting for \>7 days days without documented infection * Neutropenia Grade ≥3 with documented infection * Grade ≥3 febrile neutropenia * Grade 4 neutropenia defined as life-threatening consequences or urgent intervention indicated * Grade 5 neutropenia defined as a fatal neutropenia * Grade 3 thrombocytopenia associated with bleeding
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Population: Treated Set (TS): This set included all patients who were dispensed trial medication (BI 3011441) and were documented to have taken at least 1 dose of open-label trial medication (BI 3011441).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg BI 3011441 | Number of Patients With DLTs During the Entire On-treatment Period | 0 Participants |
| 6 mg BI 3011441Edit | Number of Patients With DLTs During the Entire On-treatment Period | 0 Participants |
| 8 mg BI 3011441 | Number of Patients With DLTs During the Entire On-treatment Period | 2 Participants |
Secondary
Number of Patients With Grade ≥3 Treatment-related Adverse Events
Number of participants with Grade ≥3 treatment-related adverse events is reported. The severity of AEs were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The CTCAE grades are Grade 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Population: Treated Set (TS): This set included all patients who were dispensed trial medication (BI 3011441) and were documented to have taken at least 1 dose of open-label trial medication (BI 3011441).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 4 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 5 | 1 Participants |
| 4 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 4 | 0 Participants |
| 4 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 3 | 1 Participants |
| 6 mg BI 3011441Edit | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 5 | 0 Participants |
| 6 mg BI 3011441Edit | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 3 | 4 Participants |
| 6 mg BI 3011441Edit | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 4 | 0 Participants |
| 8 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 4 | 1 Participants |
| 8 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 3 | 6 Participants |
| 8 mg BI 3011441 | Number of Patients With Grade ≥3 Treatment-related Adverse Events | Grade 5 | 0 Participants |
Secondary
Number of Patients With Treatment Related Adverse Events
Number of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.
Time frame: From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days.
Population: Treated Set (TS): This set included all patients who were dispensed trial medication (BI 3011441) and were documented to have taken at least 1 dose of open-label trial medication (BI 3011441).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4 mg BI 3011441 | Number of Patients With Treatment Related Adverse Events | 3 Participants |
| 6 mg BI 3011441Edit | Number of Patients With Treatment Related Adverse Events | 3 Participants |
| 8 mg BI 3011441 | Number of Patients With Treatment Related Adverse Events | 8 Participants |