Trial Outcomes & Findings for First-in-Man, Dose-escalation Trial of C-met Kinase Inhibitor MSC2156119J in Subjects With Advanced Solid Tumors (NCT NCT01014936)

Last Updated: 2022-08-24

Results Overview

DLT was defined as one of the following adverse events (AEs) observed during Cycle1, regardless of MSC2156119J relationship, excluding AEs assessed by investigator exclusively related to subject's underlying disease or medical condition: Grade 4 neutropenia for \>7 days; Grade \>=3 febrile neutropenia for \>1 day; Grade 4 thrombocytopenia/Grade 3 with bleeding; Grade \>=3 nausea and emesis, despite optimal treatment; Grade \>=3 non-hematological AE, except emesis and nausea with no adequate therapy and alopecia, Grade \>= 3 liver AE with a recovery period of \>7 days or to Grade \<=1 for subjects without liver metastases or to \<=2 for subjects with liver metastases; Grade \>=3 lipase and/or amylase rise with pancreatitis confirmation, either based on clinical or radiological signs. Any AE not otherwise defined as a DLT that, due to prolonged recovery to Grade \<=1 or baseline status, leads to delay of above 21 days in planned administration of study drug.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

149 participants

Primary outcome timeframe

Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2)

Results posted on

2022-08-24

Participant Flow

First/last subject (informed consent): November 2009/December 2014. Last subject completed: October 2015. Clinical data cut-off: February 2016

Participant milestones

Participant milestones
Measure	MSC2156119J Regimen 1 Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.
Overall Study STARTED	42	45	62
Overall Study COMPLETED	42	45	62
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

First-in-Man, Dose-escalation Trial of C-met Kinase Inhibitor MSC2156119J in Subjects With Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	Total n=149 Participants Total of all reporting groups
Age, Continuous	59.97 years STANDARD_DEVIATION 13.496 • n=5 Participants	59.29 years STANDARD_DEVIATION 14.656 • n=7 Participants	56.49 years STANDARD_DEVIATION 13.986 • n=5 Participants	58.32 years STANDARD_DEVIATION 14.050 • n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	23 Participants n=7 Participants	25 Participants n=5 Participants	66 Participants n=4 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	22 Participants n=7 Participants	37 Participants n=5 Participants	83 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2)

Population: DLT analysis set comprised of subjects who had either completed Cycle 1 or had stopped treatment because of a DLT during Cycle 1.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=21 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Number of Subjects With Any Dose Limiting Toxicity (DLT)	1 subjects	3 subjects	2 subjects	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (Day 1 to Day 21)

Population: DLT analysis set comprised of subjects who had either completed Cycle 1 or had stopped treatment because of a DLT during Cycle 1.

MTD was defined as the dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT. The primary endpoint was to determine MTD of MSC2156119J for each of the 3 treatment regimens in subjects with advanced solid tumors. However, during the course of the trial it was established that the MTD could not be determined and instead, RP2D was to be determined.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=105 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Recommended Phase 2 Dose (RP2D)	500 milligram	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline up to 158.01 weeks

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.

Related AE was defined as any untoward medical occurrence which was considered to have a relationship with the study drug (suspected to be reasonably related to the study drug or AE was medically (pharmacologically/clinically) attributed to the study drug as per Investigator's assessment.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Number of Subjects With Treatment-Related Adverse Events	14 subjects	23 subjects	39 subjects	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 158.01 weeks

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.

AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 33 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAEs	41 subjects	45 subjects	59 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death Serious TEAEs	14 subjects	17 subjects	22 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAEs Leading to Discontinuation	3 subjects	4 subjects	13 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death TEAEs Leading To Death	0 subjects	0 subjects	1 subjects	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: Pharmacokinetic (PK) analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1	56.62 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 20.4	70.65 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 19.3	107.0 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 29.6	147.0 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 24.0	193.8 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 55.3	306.4 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 42.2	348.1 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 18.6	3.445 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 104.5	12.64 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 44.5	13.72 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 142.0	13.38 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 74.1	29.03 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 94.1

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=7 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2	55.55 ng/mL Geometric Coefficient of Variation 53.6	115.5 ng/mL Geometric Coefficient of Variation 59.3	134.8 ng/mL Geometric Coefficient of Variation 22.3	142.4 ng/mL Geometric Coefficient of Variation 58.9	333.7 ng/mL Geometric Coefficient of Variation 78.5	5.926 ng/mL Geometric Coefficient of Variation 102.3	10.79 ng/mL Geometric Coefficient of Variation 67.1	22.24 ng/mL Geometric Coefficient of Variation 141.0	37.42 ng/mL Geometric Coefficient of Variation 64.4	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=19 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=7 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=1 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=22 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3	246.5 ng/mL Geometric Coefficient of Variation 32.7	552.0 ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	329.9 ng/mL Geometric Coefficient of Variation 72.4	433.5 ng/mL Geometric Coefficient of Variation 27.6	666.1 ng/mL Geometric Coefficient of Variation 46.0	761.0 ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	863.4 ng/mL Geometric Coefficient of Variation 37.4	460.9 ng/mL Geometric Coefficient of Variation 58.7	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose. Here, "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=2 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=3 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1	112.6 ng/mL Geometric Coefficient of Variation 26.1	204.6 ng/mL Geometric Coefficient of Variation 24.2	262.8 ng/mL Geometric Coefficient of Variation 10.2	379.3 ng/mL Geometric Coefficient of Variation 19.8	697.2 ng/mL Geometric Coefficient of Variation 49.8	810.9 ng/mL Geometric Coefficient of Variation 12.3	562.5 ng/mL Geometric Coefficient of Variation 45.0	28.54 ng/mL Geometric Coefficient of Variation 181.7	59.76 ng/mL Geometric Coefficient of Variation 110.0	48.33 ng/mL Geometric Coefficient of Variation 102.8	155.6 ng/mL Geometric Coefficient of Variation 249.6	210.1 ng/mL Geometric Coefficient of Variation 54.8

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2	88.55 ng/mL Geometric Coefficient of Variation 53.0	181.4 ng/mL Geometric Coefficient of Variation 34.4	178.4 ng/mL Geometric Coefficient of Variation 67.6	300.5 ng/mL Geometric Coefficient of Variation 8.9	722.4 ng/mL Geometric Coefficient of Variation 32.2	8.458 ng/mL Geometric Coefficient of Variation 339.9	54.30 ng/mL Geometric Coefficient of Variation 48.5	52.30 ng/mL Geometric Coefficient of Variation 140.7	70.04 ng/mL Geometric Coefficient of Variation 68.5	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=17 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=18 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3	741.6 ng/mL Geometric Coefficient of Variation 45.7	795.0 ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	943.1 ng/mL Geometric Coefficient of Variation 34.6	1006 ng/mL Geometric Coefficient of Variation 39.4	1219 ng/mL Geometric Coefficient of Variation 59.2	1805 ng/mL Geometric Coefficient of Variation 31.2	1291 ng/mL Geometric Coefficient of Variation 48.1	—	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1	8.000 hours Interval 2.0 to 24.05	10.000 hours Interval 8.0 to 24.0	10.000 hours Interval 4.0 to 24.0	8.000 hours Interval 8.0 to 10.0	8.000 hours Interval 4.0 to 24.0	10.000 hours Interval 4.1 to 24.0	8.000 hours Interval 8.0 to 10.05	4.000 hours Interval 4.0 to 10.0	8.000 hours Interval 8.0 to 24.0	10.000 hours Interval 4.0 to 24.0	24.000 hours Interval 8.0 to 25.65	8.000 hours Interval 4.0 to 24.0

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=7 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2	9.000 hours Interval 4.0 to 24.2	8.000 hours Interval 4.0 to 23.83	9.000 hours Interval 4.03 to 24.33	8.000 hours Interval 4.0 to 24.03	24.000 hours Interval 7.97 to 24.03	10.000 hours Interval 8.0 to 48.0	17.042 hours Interval 8.0 to 48.0	33.083 hours Interval 8.0 to 48.0	24.000 hours Interval 8.0 to 49.32	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=19 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=7 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=1 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=22 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3	8.000 hours Interval 8.0 to 24.0	8.000 hours Interval 8.0 to 8.0	10.000 hours Interval 4.0 to 24.0	10.000 hours Interval 4.0 to 24.0	10.000 hours Interval 4.0 to 10.17	10.000 hours Interval 10.0 to 10.0	24.000 hours Interval 8.0 to 24.0	8.025 hours Interval 4.0 to 24.1	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=2 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=3 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1	2.125 hours Interval 0.0 to 4.25	8.000 hours Interval 4.03 to 8.0	8.000 hours Interval 4.0 to 24.0	4.000 hours Interval 0.0 to 24.0	8.000 hours Interval 4.0 to 8.0	8.000 hours Interval 0.0 to 10.15	0.250 hours Interval 0.0 to 10.0	4.000 hours Interval 0.0 to 24.0	4.000 hours Interval 0.0 to 8.0	6.000 hours Interval 0.0 to 24.0	0.00 hours Interval 0.0 to 0.0	4.000 hours Interval 1.0 to 10.0

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2	10.000 hours Interval 4.12 to 10.08	10.000 hours Interval 2.0 to 24.13	8.000 hours Interval 4.0 to 10.0	10.000 hours Interval 8.0 to 10.0	8.000 hours Interval 8.0 to 25.93	8.000 hours Interval 8.0 to 24.0	8.067 hours Interval 4.0 to 24.0	17.083 hours Interval 8.0 to 24.08	10.000 hours Interval 8.0 to 24.12	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=17 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=18 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3	10.000 hours Interval 0.5 to 10.0	10.000 hours Interval 10.0 to 10.0	8.000 hours Interval 0.0 to 24.0	3.183 hours Interval 0.25 to 8.0	8.833 hours Interval 0.0 to 24.0	9.075 hours Interval 2.83 to 24.0	8.000 hours Interval 2.0 to 24.0	—	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant, which is needed for the calculation of t1/2.

Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1	849.4 h*ng/mL Geometric Coefficient of Variation 24.5	1283.0 h*ng/mL Geometric Coefficient of Variation 23.9	1433.5 h*ng/mL Geometric Coefficient of Variation 35.5	2532.7 h*ng/mL Geometric Coefficient of Variation 12.6	3105.5 h*ng/mL Geometric Coefficient of Variation 60.3	5467.9 h*ng/mL Geometric Coefficient of Variation 49.9	6176.3 h*ng/mL Geometric Coefficient of Variation 17.8	41.6 h*ng/mL Geometric Coefficient of Variation 288.7	218.8 h*ng/mL Geometric Coefficient of Variation 38.5	215.0 h*ng/mL Geometric Coefficient of Variation 163.5	225.6 h*ng/mL Geometric Coefficient of Variation 88.7	516.5 h*ng/mL Geometric Coefficient of Variation 74.3

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=7 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 2	1771.5 h*ng/mL Geometric Coefficient of Variation 43.1	3665.3 h*ng/mL Geometric Coefficient of Variation 41.9	3794.2 h*ng/mL Geometric Coefficient of Variation 32.1	4659.6 h*ng/mL Geometric Coefficient of Variation 44.9	10818.0 h*ng/mL Geometric Coefficient of Variation 48.9	206.9 h*ng/mL Geometric Coefficient of Variation 92.6	310.5 h*ng/mL Geometric Coefficient of Variation 27.6	745.3 h*ng/mL Geometric Coefficient of Variation 130.8	1323.5 h*ng/mL Geometric Coefficient of Variation 57.3	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=19 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=7 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=1 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=22 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 3	4209.3 h*ng/mL Geometric Coefficient of Variation 33.4	3190.8 h*ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	5667.3 h*ng/mL Geometric Coefficient of Variation 76.1	4980.9 h*ng/mL Geometric Coefficient of Variation 86.3	10355.6 h*ng/mL Geometric Coefficient of Variation 59.6	13352.6 h*ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	15542.0 h*ng/mL Geometric Coefficient of Variation 41.9	7661.8 h*ng/mL Geometric Coefficient of Variation 66.7	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=2 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=3 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 1	7532.7 h*ng/mL Geometric Coefficient of Variation 19.1	14113.2 h*ng/mL Geometric Coefficient of Variation 32.1	18334.0 h*ng/mL Geometric Coefficient of Variation 19.4	18409.6 h*ng/mL Geometric Coefficient of Variation 14.3	56102.4 h*ng/mL Geometric Coefficient of Variation 73.7	82253.4 h*ng/mL Geometric Coefficient of Variation 10.1	44598.2 h*ng/mL Geometric Coefficient of Variation 80.7	2008.0 h*ng/mL Geometric Coefficient of Variation 344.0	4483.4 h*ng/mL Geometric Coefficient of Variation 284.9	3555.4 h*ng/mL Geometric Coefficient of Variation 116.3	4234.1 h*ng/mL Geometric Coefficient of Variation 40.3	13872.2 h*ng/mL Geometric Coefficient of Variation 62.3

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 2	4079.6 h*ng/mL Geometric Coefficient of Variation 71.1	5079.7 h*ng/mL Geometric Coefficient of Variation 116.0	4962.0 h*ng/mL Geometric Coefficient of Variation 33.3	7963.8 h*ng/mL Geometric Coefficient of Variation 34.0	36701.1 h*ng/mL Geometric Coefficient of Variation 26.1	375.2 h*ng/mL Geometric Coefficient of Variation 278.2	2056.6 h*ng/mL Geometric Coefficient of Variation 31.4	2562.0 h*ng/mL Geometric Coefficient of Variation 78.9	2899.0 h*ng/mL Geometric Coefficient of Variation 132.4	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose.

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=17 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=18 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 3	15694.9 h*ng/mL Geometric Coefficient of Variation 50.8	17498.1 h*ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	20210.4 h*ng/mL Geometric Coefficient of Variation 33.5	17107.8 h*ng/mL Geometric Coefficient of Variation 3.2	27716.9 h*ng/mL Geometric Coefficient of Variation 58.6	39730.6 h*ng/mL Geometric Coefficient of Variation 29.5	18915.7 h*ng/mL Geometric Coefficient of Variation 87.5	—	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=2 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=2 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=5 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1	848.7 h*ng/mL Geometric Coefficient of Variation 24.3	1283.0 h*ng/mL Geometric Coefficient of Variation 23.9	1731.3 h*ng/mL Geometric Coefficient of Variation 14.9	2454.5 h*ng/mL Geometric Coefficient of Variation 15.4	3090.2 h*ng/mL Geometric Coefficient of Variation 61.2	5462.8 h*ng/mL Geometric Coefficient of Variation 49.9	6176.3 h*ng/mL Geometric Coefficient of Variation 17.8	94.0 h*ng/mL Geometric Coefficient of Variation 66.2	218.8 h*ng/mL Geometric Coefficient of Variation 38.5	259.3 h*ng/mL Geometric Coefficient of Variation 170.5	220.6 h*ng/mL Geometric Coefficient of Variation 93.4	515.3 h*ng/mL Geometric Coefficient of Variation 74.4

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1

Population: PK analysis set included all subjects who had received at least 1 dose of MSC2156119J and who had provided at least 1 concentration of MSC2156119J measurement after the first dose. Here, "Number Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=6 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=6 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=4 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=7 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2	1771.5 h*ng/mL Geometric Coefficient of Variation 43.1	3657.3 h*ng/mL Geometric Coefficient of Variation 42.0	3794.2 h*ng/mL Geometric Coefficient of Variation 32.1	4659.6 h*ng/mL Geometric Coefficient of Variation 44.9	10786.4 h*ng/mL Geometric Coefficient of Variation 49.4	206.9 h*ng/mL Geometric Coefficient of Variation 92.6	306.1 h*ng/mL Geometric Coefficient of Variation 33.9	626.0 h*ng/mL Geometric Coefficient of Variation 96.5	1317.0 h*ng/mL Geometric Coefficient of Variation 58.3	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=18 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=2 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=1 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=22 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3	4206.5 h*ng/mL Geometric Coefficient of Variation 33.5	NA h*ng/mL Geometric Coefficient of Variation NA Data were not reported to reduce misunderstanding as 1 subject in "MSC2156119J 500 mg: Fasted arm" either took a wrong dose or intake was performed with a wrong mode of administration.	5917.9 h*ng/mL Geometric Coefficient of Variation 74.8	7575.8 h*ng/mL Geometric Coefficient of Variation 24.6	11796.4 h*ng/mL Geometric Coefficient of Variation 48.1	NA h*ng/mL Geometric Coefficient of Variation NA Data were not reported to reduce misunderstanding as 1 subject in "MSC2156119J 1200 mg: Fasted arm" either took a wrong dose or intake was performed with a wrong mode of administration.	15542.0 h*ng/mL Geometric Coefficient of Variation 41.9	7637.3 h*ng/mL Geometric Coefficient of Variation 66.7	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=2 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=3 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted n=6 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed n=3 Participants Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted n=3 Participants Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1	2266.7 h*ng/mL Geometric Coefficient of Variation 29.5	4443.1 h*ng/mL Geometric Coefficient of Variation 28.1	5499.6 h*ng/mL Geometric Coefficient of Variation 7.0	8099.6 h*ng/mL Geometric Coefficient of Variation 18.0	13938.4 h*ng/mL Geometric Coefficient of Variation 50.9	18276.5 h*ng/mL Geometric Coefficient of Variation 12.4	12256.8 h*ng/mL Geometric Coefficient of Variation 49.1	585.3 h*ng/mL Geometric Coefficient of Variation 158.4	1241.2 h*ng/mL Geometric Coefficient of Variation 132.2	1011.1 h*ng/mL Geometric Coefficient of Variation 110.3	1434.2 h*ng/mL Geometric Coefficient of Variation 14.3	4658.2 h*ng/mL Geometric Coefficient of Variation 52.4

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=5 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=4 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=5 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=1 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=2 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted n=5 Participants Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted n=4 Participants Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2	3031.7 h*ng/mL Geometric Coefficient of Variation 55.8	7565.6 h*ng/mL Geometric Coefficient of Variation 35.0	5305.5 h*ng/mL Geometric Coefficient of Variation 62.6	9051.1 h*ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	27760.2 h*ng/mL Geometric Coefficient of Variation 25.1	273.7 h*ng/mL Geometric Coefficient of Variation 909.0	2054.1 h*ng/mL Geometric Coefficient of Variation 33.3	1634.4 h*ng/mL Geometric Coefficient of Variation 103.5	3538.9 h*ng/mL Geometric Coefficient of Variation 64.9	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=3 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=1 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=17 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed n=3 Participants Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed n=6 Participants Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed n=4 Participants Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed n=13 Participants Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3	15597.6 h*ng/mL Geometric Coefficient of Variation 50.0	17498.1 h*ng/mL Geometric Coefficient of Variation NA Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.	20169.3 h*ng/mL Geometric Coefficient of Variation 33.5	21972.2 h*ng/mL Geometric Coefficient of Variation 42.9	27214.4 h*ng/mL Geometric Coefficient of Variation 59.4	39283.7 h*ng/mL Geometric Coefficient of Variation 28.0	27437.7 h*ng/mL Geometric Coefficient of Variation 51.7	—	—	—	—	—

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Population: It was not possible to calculate data for this outcome measure because dosing interval was too small compared to the long half-life to characterize the terminal phase rate constant.

Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 1 Cycle 2

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment. Here, "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Histo score (H-score) is a composite score that comprises of intensity and percentage of staining and is used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=17 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=21 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=32 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 Cytoplasm H-Score	-12.94 units on a scale Standard Deviation 84.614	-31.43 units on a scale Standard Deviation 92.967	5.00 units on a scale Standard Deviation 72.513	—	—	—	—	—	—	—	—	—
Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 Membrane H-Score	3.53 units on a scale Standard Deviation 123.184	28.10 units on a scale Standard Deviation 75.407	-10.00 units on a scale Standard Deviation 75.818	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1 Cycle 2

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment. Here "Number of Participants analyzed" signifies those subjects who were evaluable for this outcome and "n" signifies those subjects who were evaluable in the specified category for each arm, respectively.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=16 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=17 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=30 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 Cytoplasm H-Score (n=16, 17, 30)	1.05 fold change Standard Deviation 0.577	1.09 fold change Standard Deviation 0.570	1.12 fold change Standard Deviation 0.551	—	—	—	—	—	—	—	—	—
Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 Membrane H-Score (n= 0, 4, 5)	NA fold change Standard Deviation NA Fold change could not be calculated as there were no subjects with H-score baseline value of greater than 0.	1.29 fold change Standard Deviation 0.934	1.23 fold change Standard Deviation 0.541	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 Cycle 2

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.

MetMAb score was used to assess the tumor c-Met expression and ranged from 0 to 3, where a score of 0 corresponds to the lowest c-Met expression and a score of 3 corresponds to the highest c-Met expression in tumor tissue by immunohistochemistry.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) MMS Score Missing	24 subjects	21 subjects	27 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) MMS Score 0	3 subjects	5 subjects	1 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) MMS Score 1	9 subjects	7 subjects	12 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) MMS Score 2	4 subjects	10 subjects	14 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) MMS Score 3	2 subjects	2 subjects	8 subjects	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, On Treatment (up to 153.3 weeks)

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment. Here "Number of Participants Analyzed" signifies those subjects who presented a measurable tumor at baseline and at least one post-baseline tumor assessment.

The post-baseline nadir was defined as the the smallest SOLD recorded after baseline. The relative change (%) was derived based on the SOLD of target lesions as follows: 100\* (SOLD at post-baseline nadir - baseline SOLD) / baseline SOLD.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=35 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=36 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=52 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Relative Percentage Change In Sum of Longest Diameter (SOLD) of Target Lesions to Post-Baseline Nadir	25.67 percent change Standard Deviation 28.738	16.19 percent change Standard Deviation 22.055	18.87 percent change Standard Deviation 39.464	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 153.3 weeks

Population: Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.

Number of subjects with BOR in each category (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: defined as at least a 30% decrease in sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD:defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=42 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Number of Subjects With Best Overall Response (BOR) PR	0 subjects	0 subjects	2 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Best Overall Response (BOR) CR	0 subjects	0 subjects	0 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Best Overall Response (BOR) SD	12 subjects	10 subjects	12 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Best Overall Response (BOR) PD	25 subjects	27 subjects	38 subjects	—	—	—	—	—	—	—	—	—
Number of Subjects With Best Overall Response (BOR) Not evaluable	5 subjects	8 subjects	10 subjects	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 153.3 weeks

PFS was defined as the time (in months) between the first dosing day and radiographic PD or clinical PD (as recorded on the study termination form) or death, if death occurred within 12 weeks (84 days) after the last tumor assessment without documented progressive disease, whichever occurred first. Any subject with neither assessment of tumor progression, nor death within 12 weeks after last tumor assessment date was censored on the date of last tumor assessment.

Outcome measures

Outcome measures
Measure	MSC2156119J Regimen 1 n=41 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 Participants Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 Participants Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.	MSC2156119J 145 mg: Fed Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.	MSC2156119J 215 mg: Fed Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.	MSC2156119J 300 mg: Fed Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.	MSC2156119J 400 mg: Fed Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.	MSC2156119J 30 mg: Fasted Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.	MSC2156119J 60 mg: Fasted Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fasted Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.	MSC2156119J 115 mg: Fed Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.	MSC2156119J 230 mg: Fasted Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Progression-free Survival (PFS)	1.4 months Interval 1.3 to 1.4	1.3 months Interval 1.2 to 1.3	1.4 months Interval 1.3 to 1.4	—	—	—	—	—	—	—	—	—

Adverse Events

MSC2156119J Regimen 1

Serious events: 14 serious events

Other events: 41 other events

Deaths: 0 deaths

MSC2156119J Regimen 2

Serious events: 17 serious events

Other events: 45 other events

Deaths: 0 deaths

MSC2156119J Regimen 3

Serious events: 22 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MSC2156119J Regimen 1 n=42 participants at risk Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 participants at risk Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 participants at risk Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.
Blood and lymphatic system disorders ANAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders LEUKOCYTOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Cardiac disorders ATRIAL FIBRILLATION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Cardiac disorders TACHYCARDIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Endocrine disorders INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL PAIN	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders CONSTIPATION	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders NAUSEA	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	2.4% 1/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ASCITES	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders VOMITING	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL PAIN LOWER	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders FAECALOMA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders IMPAIRED GASTRIC EMPTYING	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders LARGE INTESTINAL OBSTRUCTION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders MESENTERIC VEIN THROMBOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders PYREXIA	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders DEVICE OCCLUSION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders DISEASE PROGRESSION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders GENERAL PHYSICAL HEALTH DETERIORATION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders OEDEMA PERIPHERAL	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders PERIPHERAL SWELLING	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders HEPATIC FAILURE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders JAUNDICE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders JAUNDICE CHOLESTATIC	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations SEPTIC SHOCK	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations STAPHYLOCOCCAL BACTERAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations ABDOMINAL WALL INFECTION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations CELLULITIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations DEVICE RELATED INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations ESCHERICHIA URINARY TRACT INFECTION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations GANGRENE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations KIDNEY INFECTION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations LOBAR PNEUMONIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations OSTEOMYELITIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations STAPHYLOCOCCAL INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations TRACHEOBRONCHITIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations URINARY TRACT INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations URINARY TRACT INFECTION STAPHYLOCOCCAL	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications HIP FRACTURE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD BILIRUBIN INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations TRANSAMINASES INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations WAIST CIRCUMFERENCE INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders FAILURE TO THRIVE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERKALAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders OSTEONECROSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO CENTRAL NERVOUS SYSTEM	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders HEADACHE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders SPINAL CORD COMPRESSION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders SYNCOPE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders VAGUS NERVE DISORDER	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Renal and urinary disorders ACUTE KIDNEY INJURY	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders HYDRONEPHROSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders URINARY INCONTINENCE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders VAGINAL HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	4.8% 2/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Vascular disorders JUGULAR VEIN THROMBOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Vascular disorders SUPERIOR VENA CAVA SYNDROME	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks

Other adverse events

Other adverse events
Measure	MSC2156119J Regimen 1 n=42 participants at risk Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.	MSC2156119J Regimen 2 n=45 participants at risk Subjects were administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.	MSC2156119J Regimen 3 n=62 participants at risk Subjects were administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.
Blood and lymphatic system disorders ANAEMIA	9.5% 4/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	11.3% 7/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders LEUKOCYTOSIS	4.8% 2/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders THROMBOCYTOPENIA	9.5% 4/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders NEUTROPENIA	0.00% 0/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders LEUKOPENIA	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders ANAEMIA OF CHRONIC DISEASE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders HAEMOLYTIC ANAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders HAEMORRHAGIC ANAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Blood and lymphatic system disorders THROMBOCYTOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Cardiac disorders TACHYCARDIA	4.8% 2/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	8.1% 5/62 • Baseline up to 158.01 weeks
Cardiac disorders ATRIAL FIBRILLATION	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Cardiac disorders ANGINA PECTORIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Cardiac disorders BRADYCARDIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Cardiac disorders SINUS ARRHYTHMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders DEAFNESS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders EAR DISCOMFORT	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders EAR PAIN	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders EAR SWELLING	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders MIDDLE EAR EFFUSION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders VERTIGO	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Ear and labyrinth disorders VERTIGO POSITIONAL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Endocrine disorders HYPOTHYROIDISM	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Endocrine disorders BASEDOW'S DISEASE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Endocrine disorders THYROID DISORDER	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Eye disorders VISION BLURRED	4.8% 2/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Eye disorders DRY EYE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Eye disorders LACRIMATION INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Eye disorders BLEPHAROSPASM	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Eye disorders RETINAL PIGMENT EPITHELIOPATHY	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Eye disorders VISUAL ACUITY REDUCED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Eye disorders VITREOUS FLOATERS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders CONSTIPATION	28.6% 12/42 • Baseline up to 158.01 weeks	22.2% 10/45 • Baseline up to 158.01 weeks	25.8% 16/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders NAUSEA	26.2% 11/42 • Baseline up to 158.01 weeks	22.2% 10/45 • Baseline up to 158.01 weeks	17.7% 11/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders VOMITING	26.2% 11/42 • Baseline up to 158.01 weeks	17.8% 8/45 • Baseline up to 158.01 weeks	16.1% 10/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL PAIN	9.5% 4/42 • Baseline up to 158.01 weeks	15.6% 7/45 • Baseline up to 158.01 weeks	14.5% 9/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders DIARRHOEA	16.7% 7/42 • Baseline up to 158.01 weeks	13.3% 6/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL DISTENSION	4.8% 2/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ASCITES	2.4% 1/42 • Baseline up to 158.01 weeks	13.3% 6/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders DRY MOUTH	4.8% 2/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	8.1% 5/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL PAIN UPPER	0.00% 0/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders DYSPHAGIA	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	9.5% 4/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders HAEMORRHOIDS	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders DYSPEPSIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders MELAENA	4.8% 2/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders STOMATITIS	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL DISCOMFORT	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ABDOMINAL MASS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders CHANGE OF BOWEL HABIT	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ERUCTATION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders FAECAL INCONTINENCE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders FAECES DISCOLOURED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders FLATULENCE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GASTROINTESTINAL MOTILITY DISORDER	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GASTROINTESTINAL SOUNDS ABNORMAL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders GINGIVAL PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders HAEMATOCHEZIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders LIP SWELLING	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders NEUROGENIC BOWEL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders ODYNOPHAGIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders RETCHING	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Gastrointestinal disorders TOOTHACHE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders FATIGUE	28.6% 12/42 • Baseline up to 158.01 weeks	37.8% 17/45 • Baseline up to 158.01 weeks	32.3% 20/62 • Baseline up to 158.01 weeks
General disorders OEDEMA PERIPHERAL	14.3% 6/42 • Baseline up to 158.01 weeks	20.0% 9/45 • Baseline up to 158.01 weeks	38.7% 24/62 • Baseline up to 158.01 weeks
General disorders PYREXIA	11.9% 5/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
General disorders CHILLS	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
General disorders NON-CARDIAC CHEST PAIN	2.4% 1/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders MALAISE	0.00% 0/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders PERIPHERAL SWELLING	7.1% 3/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders ASTHENIA	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders AXILLARY PAIN	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders EARLY SATIETY	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
General disorders GAIT DISTURBANCE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
General disorders LOCAL SWELLING	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders OEDEMA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
General disorders CATHETER SITE ERYTHEMA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
General disorders FEELING COLD	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders GENERALISED OEDEMA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders LOCALISED OEDEMA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
General disorders SENSATION OF FOREIGN BODY	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders HYPERBILIRUBINAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders JAUNDICE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Hepatobiliary disorders PORTAL VEIN THROMBOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Immune system disorders ALLERGY TO ARTHROPOD BITE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations URINARY TRACT INFECTION	4.8% 2/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	11.3% 7/62 • Baseline up to 158.01 weeks
Infections and infestations ORAL CANDIDIASIS	2.4% 1/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Infections and infestations PNEUMONIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Infections and infestations SINUSITIS	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations FUNGAL INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	4.8% 2/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations STAPHYLOCOCCAL INFECTION	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations BRONCHITIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations CELLULITIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations CONJUNCTIVITIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations DEVICE RELATED INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations EAR INFECTION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations HORDEOLUM	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations INFECTED FISTULA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations NAIL BED INFECTION FUNGAL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations ONYCHOMYCOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations PAROTITIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations POST PROCEDURAL INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations TOOTH ABSCESS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations UPPER RESPIRATORY TRACT INFECTION BACTERIAL	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Infections and infestations UROSEPSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Infections and infestations WOUND INFECTION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications FALL	0.00% 0/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications ANKLE FRACTURE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications CONTUSION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications EPICONDYLITIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications FEEDING TUBE COMPLICATION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications JOINT INJURY	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications LACERATION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications LIMB INJURY	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications NAIL INJURY	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications PROCEDURAL HAEMORRHAGE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications RADIATION PNEUMONITIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Injury, poisoning and procedural complications STOMA SITE HAEMORRHAGE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	16.7% 7/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	12.9% 8/62 • Baseline up to 158.01 weeks
Investigations LIPASE INCREASED	7.1% 3/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Investigations TRANSAMINASES INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	11.3% 7/62 • Baseline up to 158.01 weeks
Investigations ALANINE AMINOTRANSFERASE INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Investigations BLOOD CREATININE INCREASED	7.1% 3/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	8.1% 5/62 • Baseline up to 158.01 weeks
Investigations BLOOD BILIRUBIN INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Investigations BREATH SOUNDS ABNORMAL	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Investigations WEIGHT DECREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Investigations AMYLASE INCREASED	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Investigations HAEMOGLOBIN INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations INTERNATIONAL NORMALISED RATIO INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations PROSTATIC SPECIFIC ANTIGEN INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Investigations WEIGHT INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations ANTICOAGULATION DRUG LEVEL BELOW THERAPEUTIC	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD CREATINE INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations BLOOD GLUCOSE DECREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD GLUCOSE INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD LACTATE DEHYDROGENASE INCREASED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations BLOOD PRESSURE DIASTOLIC ABNORMAL	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations BLOOD UREA INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations ELECTROCARDIOGRAM PR SHORTENED	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations ELECTROCARDIOGRAM QT PROLONGED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations ELECTROCARDIOGRAM ST SEGMENT ELEVATION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations HAEMATOCRIT INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations NEUTROPHIL COUNT INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations PEDAL PULSE ABNORMAL	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations PLATELET COUNT DECREASED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Investigations WAIST CIRCUMFERENCE INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Investigations WHITE BLOOD CELL COUNT INCREASED	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders DECREASED APPETITE	28.6% 12/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	43.5% 27/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOALBUMINAEMIA	19.0% 8/42 • Baseline up to 158.01 weeks	13.3% 6/45 • Baseline up to 158.01 weeks	17.7% 11/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders DEHYDRATION	4.8% 2/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	14.5% 9/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPONATRAEMIA	7.1% 3/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	12.9% 8/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOMAGNESAEMIA	9.5% 4/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERKALAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Investigations HYPOKALAEMIA	7.1% 3/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOCALCAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders CACHEXIA	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERPHOSPHATAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERGLYCAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERURICAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders MALNUTRITION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders DYSLIPIDAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPERCALCAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOCHOLESTEROLAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOGLYCAEMIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOPHOSPHATAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Metabolism and nutrition disorders HYPOVOLAEMIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MYALGIA	9.5% 4/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	14.3% 6/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders ARTHRALGIA	14.3% 6/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders BACK PAIN	9.5% 4/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	4.8% 2/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	4.8% 2/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders NECK PAIN	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders PAIN IN JAW	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders BONE PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders GROIN PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders JOINT ANKYLOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders MYOPATHY	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SEBORRHOEIC KERATOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) OESOPHAGEAL CANCER METASTATIC	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR INVASION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders DIZZINESS	7.1% 3/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	11.3% 7/62 • Baseline up to 158.01 weeks
Nervous system disorders NEUROPATHY PERIPHERAL	4.8% 2/42 • Baseline up to 158.01 weeks	8.9% 4/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Nervous system disorders HEADACHE	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Nervous system disorders MEMORY IMPAIRMENT	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders DYSGEUSIA	0.00% 0/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders SOMNOLENCE	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Nervous system disorders HYPOAESTHESIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders PARAESTHESIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders SYNCOPE	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders TREMOR	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders AKATHISIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders BALANCE DISORDER	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders DIZZINESS POSTURAL	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders DYSKINESIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders HYPOGEUSIA	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders LETHARGY	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders NEURALGIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders SPINAL CORD COMPRESSION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Nervous system disorders VIITH NERVE PARALYSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Nervous system disorders VOCAL CORD PARALYSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Psychiatric disorders INSOMNIA	9.5% 4/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Psychiatric disorders ANXIETY	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Psychiatric disorders AGITATION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Psychiatric disorders DELIRIUM	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Psychiatric disorders DEPRESSION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Psychiatric disorders DISORIENTATION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Psychiatric disorders EMOTIONAL DISTRESS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Psychiatric disorders FLAT AFFECT	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Psychiatric disorders RESTLESSNESS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders RENAL FAILURE	7.1% 3/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	6.5% 4/62 • Baseline up to 158.01 weeks
Renal and urinary disorders PROTEINURIA	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders ACUTE KIDNEY INJURY	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders DYSURIA	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders CHROMATURIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders GLYCOSURIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders HAEMATURIA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders HYDRONEPHROSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders NEUROGENIC BLADDER	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders NOCTURIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders POLLAKIURIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders RENAL ATROPHY	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders RENAL HYPERTROPHY	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders RENAL IMPAIRMENT	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders URETERIC OBSTRUCTION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Renal and urinary disorders URINARY HESITATION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Renal and urinary disorders URINARY RETENTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders SCROTAL OEDEMA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders NIPPLE PAIN	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders VAGINAL DISCHARGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders VAGINAL HAEMORRHAGE	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders BREAST MASS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders BREAST SWELLING	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders BREAST TENDERNESS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders DYSPAREUNIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders NIPPLE DISORDER	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders PENILE OEDEMA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders SCROTAL SWELLING	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Reproductive system and breast disorders TESTICULAR SWELLING	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders DYSPNOEA	4.8% 2/42 • Baseline up to 158.01 weeks	11.1% 5/45 • Baseline up to 158.01 weeks	19.4% 12/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	7.1% 3/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	9.7% 6/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders COUGH	9.5% 4/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	7.1% 3/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders HICCUPS	2.4% 1/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	4.8% 2/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	0.00% 0/42 • Baseline up to 158.01 weeks	4.4% 2/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders RHINORRHOEA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders ASPIRATION	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders ATELECTASIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders PULMONARY OEDEMA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders RESPIRATORY TRACT CONGESTION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders TACHYPNOEA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Respiratory, thoracic and mediastinal disorders WHEEZING	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH	7.1% 3/42 • Baseline up to 158.01 weeks	6.7% 3/45 • Baseline up to 158.01 weeks	8.1% 5/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders ALOPECIA	4.8% 2/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders DRY SKIN	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders ERYTHEMA	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders HYPERHIDROSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders NAIL DISORDER	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders NIGHT SWEATS	4.8% 2/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders PHOTOSENSITIVITY REACTION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders PRURITUS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH ERYTHEMATOUS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH VESICULAR	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SKIN HYPERPIGMENTATION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SWELLING FACE	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders ACTINIC KERATOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders BLISTER	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders HYPERKERATOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders INGROWING NAIL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders ONYCHOCLASIS	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders ONYCHOLYSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH GENERALISED	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH MACULO-PAPULAR	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders RASH PRURITIC	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SKIN EXFOLIATION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SKIN LESION	0.00% 0/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SKIN MASS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders SKIN ULCER	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders STASIS DERMATITIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Skin and subcutaneous tissue disorders URTICARIA	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Vascular disorders DEEP VEIN THROMBOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	4.8% 3/62 • Baseline up to 158.01 weeks
Vascular disorders HYPOTENSION	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	3.2% 2/62 • Baseline up to 158.01 weeks
Vascular disorders HYPERTENSION	2.4% 1/42 • Baseline up to 158.01 weeks	2.2% 1/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Vascular disorders HOT FLUSH	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Vascular disorders SUBCLAVIAN VEIN THROMBOSIS	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Vascular disorders THROMBOPHLEBITIS SUPERFICIAL	2.4% 1/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	0.00% 0/62 • Baseline up to 158.01 weeks
Vascular disorders THROMBOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks
Vascular disorders VENOUS THROMBOSIS	0.00% 0/42 • Baseline up to 158.01 weeks	0.00% 0/45 • Baseline up to 158.01 weeks	1.6% 1/62 • Baseline up to 158.01 weeks

Additional Information

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Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place