Trial Outcomes & Findings for A Study to Test Different Doses of BI 3011441 in Japanese People With Different Types of Advanced Cancer (NRAS/KRAS Mutation Positive) (NCT NCT04742556)

Last Updated: 2024-09-19

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

First treatment cycle, the first 28 days following the start of trial medication.

Results posted on

2024-09-19

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	3	4	8
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Withdrawal by Subject	0	1	0
Overall Study Adverse Event	0	0	2
Overall Study Clinical disease progression	0	1	2
Overall Study Objective disease progression	3	2	4

Baseline Characteristics

A Study to Test Different Doses of BI 3011441 in Japanese People With Different Types of Advanced Cancer (NRAS/KRAS Mutation Positive)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441 n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.	Total n=15 Participants Total of all reporting groups
Age, Continuous	60.0 Years STANDARD_DEVIATION 13.9 • n=5 Participants	55.5 Years STANDARD_DEVIATION 13.3 • n=7 Participants	49.5 Years STANDARD_DEVIATION 13.8 • n=5 Participants	53.2 Years STANDARD_DEVIATION 13.4 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=3 Participants 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.	8 mg BI 3011441 n=6 Participants 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.
Number of Patients With DLTs in the MTD Evaluation Period	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=12 Participants 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.	6 mg BI 3011441Edit 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.	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.
Maximum Tolerated Dose (MTD) of BI 3011441 Monotherapy	NA milligram (mg) Maximum tolerated dose was not reached during the MTD evaluation period (the first 28 days of study treatment).	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.
Number of Patients With DLTs During the Entire On-treatment Period	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.
Number of Patients With Grade ≥3 Treatment-related Adverse Events Grade 3	1 Participants	4 Participants	6 Participants
Number of Patients With Grade ≥3 Treatment-related Adverse Events Grade 4	0 Participants	0 Participants	1 Participants
Number of Patients With Grade ≥3 Treatment-related Adverse Events Grade 5	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.
Number of Patients With Treatment Related Adverse Events	3 Participants	3 Participants	8 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.
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	471 hour * nanomol/ milliliter (h*nmol/mL) Geometric Coefficient of Variation 35.3	704 hour * nanomol/ milliliter (h*nmol/mL) Geometric Coefficient of Variation 39.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=2 Participants 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.	6 mg BI 3011441Edit n=3 Participants 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.	8 mg BI 3011441 n=4 Participants 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.
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	973 hour * nanomol/ milliliter (h*nmol/mL) Geometric Coefficient of Variation 22.9	833 hour * nanomol/ milliliter (h*nmol/mL) Geometric Coefficient of Variation 54.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=3 Participants 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.	6 mg BI 3011441Edit n=4 Participants 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.	8 mg BI 3011441 n=8 Participants 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.
Maximum Measured Concentration of BI 3011441 in Plasma After First Dose (Cmax)	72.3 nanomol/ liter (nmol/L) Geometric Coefficient of Variation 11.8	91.8 nanomol/ liter (nmol/L) Geometric Coefficient of Variation 27.1	133 nanomol/ liter (nmol/L) Geometric Coefficient of Variation 32.6

SECONDARY outcome

Maximum measured concentration of BI 3011441 in plasma at steady state (Cmax,ss) is reported. PK samples were collected at the following timepoints.

Outcome measures

Outcome measures
Measure	4 mg BI 3011441 n=2 Participants 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.	6 mg BI 3011441Edit n=3 Participants 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.	8 mg BI 3011441 n=4 Participants 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.
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	124 nanomol/ liter (nmol/L) Geometric Coefficient of Variation 37.2	130 nanomol/ liter (nmol/L) Geometric Coefficient of Variation 54.9

Adverse Events

4 mg BI 3011441

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

6 mg BI 3011441

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

8 mg BI 3011441

Serious events: 6 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	4 mg BI 3011441 n=3 participants at risk 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.	6 mg BI 3011441 n=4 participants at risk 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.	8 mg BI 3011441 n=8 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Eye disorders Serous retinal detachment	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Duodenal stenosis	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Haemoperitoneum	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
General disorders Fatigue	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
General disorders Pyrexia	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Hepatobiliary disorders Bile duct stenosis	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Investigations Blood creatinine increased	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	33.3% 1/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Vascular disorders Deep vein thrombosis	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	12.5% 1/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).
Vascular disorders Embolism	0.00% 0/3 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	25.0% 1/4 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).	0.00% 0/8 • From first BI 3011441 intake until last BI 3011441 intake + 30 days of Residual effect period (REP), up to 373 days. 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).