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

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ClinicalTrials.gov Identifier: NCT01014936
Recruitment Status : Completed
First Posted : November 17, 2009
Results First Posted : April 17, 2017
Last Update Posted : August 4, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available
Intervention Drug: MSC2156119J
Enrollment 149
Recruitment Details  
Pre-assignment Details First/last subject (informed consent): November 2009/December 2014. Last subject completed: October 2015. Clinical data cut-off: February 2016
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 42 45 62
Completed 42 45 62
Not Completed 0 0 0
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3 Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 42 45 62 149
Hide Baseline Analysis Population Description
Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 42 participants 45 participants 62 participants 149 participants
59.97  (13.496) 59.29  (14.656) 56.49  (13.986) 58.32  (14.050)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 42 participants 45 participants 62 participants 149 participants
Female
18
  42.9%
23
  51.1%
25
  40.3%
66
  44.3%
Male
24
  57.1%
22
  48.9%
37
  59.7%
83
  55.7%
1.Primary Outcome
Title Number of Subjects With Any Dose Limiting Toxicity (DLT)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT analysis set comprised of subjects who had either completed Cycle 1 or had stopped treatment because of a DLT during Cycle 1.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 42 21
Measure Type: Number
Unit of Measure: subjects
1 3 2
2.Primary Outcome
Title Recommended Phase 2 Dose (RP2D)
Hide Description 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.
Time Frame Cycle 1 (Day 1 to Day 21)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT analysis set comprised of subjects who had either completed Cycle 1 or had stopped treatment because of a DLT during Cycle 1.
Arm/Group Title MSC2156119J Combined
Hide Arm/Group Description:
All subjects who were administered with micronized or non-micronized MSC2156119J (capsule or tablet formulation) in any of the three regimens.
Overall Number of Participants Analyzed 105
Measure Type: Number
Unit of Measure: milligram
500
3.Primary Outcome
Title Number of Subjects With Treatment-Related Adverse Events
Hide Description 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.
Time Frame Baseline up to 158.01 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 45 62
Measure Type: Number
Unit of Measure: subjects
14 23 39
4.Secondary Outcome
Title Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
Hide Description 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.
Time Frame Baseline up to 158.01 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 45 62
Measure Type: Number
Unit of Measure: subjects
TEAEs 41 45 59
Serious TEAEs 14 17 22
TEAEs Leading to Discontinuation 3 4 13
TEAEs Leading To Death 0 0 1
5.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 3 3 3 3 3 3 3 3 3 6 6 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
56.62
(20.4%)
70.65
(19.3%)
107.0
(29.6%)
147.0
(24.0%)
193.8
(55.3%)
306.4
(42.2%)
348.1
(18.6%)
3.445
(104.5%)
12.64
(44.5%)
13.72
(142.0%)
13.38
(74.1%)
29.03
(94.1%)
6.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 6 6 6 3 4 3 4 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
55.55
(53.6%)
115.5
(59.3%)
134.8
(22.3%)
142.4
(58.9%)
333.7
(78.5%)
5.926
(102.3%)
10.79
(67.1%)
22.24
(141.0%)
37.42
(64.4%)
7.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 19 3 7 1 6 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
246.5
(32.7%)
552.0 [1] 
(NA%)
329.9
(72.4%)
433.5
(27.6%)
666.1
(46.0%)
761.0 [1] 
(NA%)
863.4
(37.4%)
460.9
(58.7%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
8.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 2 3 3 3 3 3 3 3 3 6 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
112.6
(26.1%)
204.6
(24.2%)
262.8
(10.2%)
379.3
(19.8%)
697.2
(49.8%)
810.9
(12.3%)
562.5
(45.0%)
28.54
(181.7%)
59.76
(110.0%)
48.33
(102.8%)
155.6
(249.6%)
210.1
(54.8%)
9.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 5 5 6 3 3 3 3 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
88.55
(53.0%)
181.4
(34.4%)
178.4
(67.6%)
300.5
(8.9%)
722.4
(32.2%)
8.458
(339.9%)
54.30
(48.5%)
52.30
(140.7%)
70.04
(68.5%)
10.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3
Hide Description 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".
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 17 3 6 4 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
741.6
(45.7%)
795.0 [1] 
(NA%)
943.1
(34.6%)
1006
(39.4%)
1219
(59.2%)
1805
(31.2%)
1291
(48.1%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
11.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 3 3 3 3 3 3 3 3 3 6 6 3
Median (Full Range)
Unit of Measure: hours
8.000
(2.00 to 24.05)
10.000
(8.00 to 24.00)
10.000
(4.00 to 24.00)
8.000
(8.00 to 10.00)
8.000
(4.00 to 24.00)
10.000
(4.10 to 24.00)
8.000
(8.00 to 10.05)
4.000
(4.00 to 10.00)
8.000
(8.00 to 24.00)
10.000
(4.00 to 24.00)
24.000
(8.00 to 25.65)
8.000
(4.00 to 24.00)
12.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 6 6 6 3 4 3 4 6 7
Median (Full Range)
Unit of Measure: hours
9.000
(4.00 to 24.20)
8.000
(4.000 to 23.83)
9.000
(4.03 to 24.33)
8.000
(4.00 to 24.03)
24.000
(7.97 to 24.03)
10.000
(8.00 to 48.00)
17.042
(8.00 to 48.00)
33.083
(8.00 to 48.00)
24.000
(8.00 to 49.32)
13.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 19 3 7 1 6 22
Median (Full Range)
Unit of Measure: hours
8.000
(8.00 to 24.00)
8.000
(8.00 to 8.00)
10.000
(4.00 to 24.00)
10.000
(4.00 to 24.00)
10.000
(4.00 to 10.17)
10.000
(10.00 to 10.00)
24.000
(8.00 to 24.00)
8.025
(4.00 to 24.10)
14.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 2 3 3 3 3 3 3 3 3 6 3 3
Median (Full Range)
Unit of Measure: hours
2.125
(0.00 to 4.25)
8.000
(4.03 to 8.00)
8.000
(4.00 to 24.00)
4.000
(0.00 to 24.00)
8.000
(4.00 to 8.00)
8.000
(0.00 to 10.15)
0.250
(0.00 to 10.00)
4.000
(0.00 to 24.00)
4.000
(0.00 to 8.00)
6.000
(0.00 to 24.00)
0.00
(0.00 to 0.00)
4.000
(1.00 to 10.00)
15.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 5 5 6 3 3 3 3 6 6
Median (Full Range)
Unit of Measure: hours
10.000
(4.12 to 10.08)
10.000
(2.00 to 24.13)
8.000
(4.00 to 10.00)
10.000
(8.00 to 10.00)
8.000
(8.00 to 25.93)
8.000
(8.00 to 24.00)
8.067
(4.00 to 24.00)
17.083
(8.00 to 24.08)
10.000
(8.00 to 24.12)
16.Secondary Outcome
Title Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3
Hide Description 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".
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 17 3 6 4 18
Median (Full Range)
Unit of Measure: hours
10.000
(0.50 to 10.00)
10.000
(10.00 to 10.00)
8.000
(0.00 to 24.00)
3.183
(0.25 to 8.00)
8.833
(0.00 to 24.00)
9.075
(2.83 to 24.00)
8.000
(2.00 to 24.00)
17.Secondary Outcome
Title Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
19.Secondary Outcome
Title Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg Fed MSC2156119J 500 mg Fasted MSC2156119J 500 mg Fed MSC2156119J 700 mg Fed MSC2156119J 1000 mg Fed MSC2156119J 1200 mg Fasted MSC2156119J 1400 mg Fed MSC2156119J 500 mg Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg with food.
Subjects were administered with micronized MSC2156119J 500 mg in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg with food.
Subjects were administered with micronized MSC2156119J 700 mg with food.
Subjects were administered with micronized MSC2156119J 1000 mg with food.
Subjects were administered with micronized MSC2156119J 1200 mg in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
21.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 3 3 3 3 3 3 3 3 3 6 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
849.4
(24.5%)
1283.0
(23.9%)
1433.5
(35.5%)
2532.7
(12.6%)
3105.5
(60.3%)
5467.9
(49.9%)
6176.3
(17.8%)
41.6
(288.7%)
218.8
(38.5%)
215.0
(163.5%)
225.6
(88.7%)
516.5
(74.3%)
24.Secondary Outcome
Title 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
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 6 6 6 3 4 3 4 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
1771.5
(43.1%)
3665.3
(41.9%)
3794.2
(32.1%)
4659.6
(44.9%)
10818.0
(48.9%)
206.9
(92.6%)
310.5
(27.6%)
745.3
(130.8%)
1323.5
(57.3%)
25.Secondary Outcome
Title 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
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 19 3 7 1 6 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
4209.3
(33.4%)
3190.8 [1] 
(NA%)
5667.3
(76.1%)
4980.9
(86.3%)
10355.6
(59.6%)
13352.6 [1] 
(NA%)
15542.0
(41.9%)
7661.8
(66.7%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
26.Secondary Outcome
Title 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
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 2 3 3 3 3 3 3 3 3 6 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
7532.7
(19.1%)
14113.2
(32.1%)
18334.0
(19.4%)
18409.6
(14.3%)
56102.4
(73.7%)
82253.4
(10.1%)
44598.2
(80.7%)
2008.0
(344.0%)
4483.4
(284.9%)
3555.4
(116.3%)
4234.1
(40.3%)
13872.2
(62.3%)
27.Secondary Outcome
Title 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
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 5 5 6 3 3 3 3 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
4079.6
(71.1%)
5079.7
(116.0%)
4962.0
(33.3%)
7963.8
(34.0%)
36701.1
(26.1%)
375.2
(278.2%)
2056.6
(31.4%)
2562.0
(78.9%)
2899.0
(132.4%)
28.Secondary Outcome
Title 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
Hide Description 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".
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 17 3 6 4 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
15694.9
(50.8%)
17498.1 [1] 
(NA%)
20210.4
(33.5%)
17107.8
(3.2%)
27716.9
(58.6%)
39730.6
(29.5%)
18915.7
(87.5%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
29.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 AUC0-inf.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg Fed MSC2156119J 215 mg Fed MSC2156119J 300 mg Fed MSC2156119J 400 mg Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
30.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 AUC0-inf.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
31.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 AUC0-inf.
Arm/Group Title MSC2156119J 300 mg Fed MSC2156119J 500 mg Fasted MSC2156119J 500 mg Fed MSC2156119J 700 mg Fed MSC2156119J 1000 mg Fed MSC2156119J 1200 mg Fasted MSC2156119J 1400 mg Fed MSC2156119J 500 mg Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg with food
Subjects were administered with micronized MSC2156119J 500 mg in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg with food
Subjects were administered with micronized MSC2156119J 700 mg with food.
Subjects were administered with micronized MSC2156119J 1000 mg with food.
Subjects were administered with micronized MSC2156119J 1200 mg in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg with food.
Subjects were administered with micronized MSC2156119J 500 mg (Tablet) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
32.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 3 3 2 3 3 3 3 2 3 5 6 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
848.7
(24.3%)
1283.0
(23.9%)
1731.3
(14.9%)
2454.5
(15.4%)
3090.2
(61.2%)
5462.8
(49.9%)
6176.3
(17.8%)
94.0
(66.2%)
218.8
(38.5%)
259.3
(170.5%)
220.6
(93.4%)
515.3
(74.4%)
33.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 6 6 6 3 4 3 3 4 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
1771.5
(43.1%)
3657.3
(42.0%)
3794.2
(32.1%)
4659.6
(44.9%)
10786.4
(49.4%)
206.9
(92.6%)
306.1
(33.9%)
626.0
(96.5%)
1317.0
(58.3%)
34.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 18 2 6 1 6 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
4206.5
(33.5%)
NA [1] 
(NA%)
5917.9
(74.8%)
7575.8
(24.6%)
11796.4
(48.1%)
NA [2] 
(NA%)
15542.0
(41.9%)
7637.3
(66.7%)
[1]
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.
[2]
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.
35.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 2 3 3 3 3 3 3 3 3 6 3 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
2266.7
(29.5%)
4443.1
(28.1%)
5499.6
(7.0%)
8099.6
(18.0%)
13938.4
(50.9%)
18276.5
(12.4%)
12256.8
(49.1%)
585.3
(158.4%)
1241.2
(132.2%)
1011.1
(110.3%)
1434.2
(14.3%)
4658.2
(52.4%)
36.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2
Hide Description [Not Specified]
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 5 4 5 1 3 2 3 5 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
3031.7
(55.8%)
7565.6
(35.0%)
5305.5
(62.6%)
9051.1 [1] 
(NA%)
27760.2
(25.1%)
273.7
(909.0%)
2054.1
(33.3%)
1634.4
(103.5%)
3538.9
(64.9%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
37.Secondary Outcome
Title Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3
Hide Description 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".
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 3 1 17 3 6 4 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
15597.6
(50.0%)
17498.1 [1] 
(NA%)
20169.3
(33.5%)
21972.2
(42.9%)
27214.4
(59.4%)
39283.7
(28.0%)
27437.7
(51.7%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
38.Secondary Outcome
Title Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 CL/f.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
39.Secondary Outcome
Title Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 CL/f.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
40.Secondary Outcome
Title Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 CL/f.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
41.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
42.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
43.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
44.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 1
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
45.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 2
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
46.Secondary Outcome
Title Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 3
Hide Description 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.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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 Vz/f.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
47.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 1
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
48.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 2
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
49.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 3
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1200 mg: Fasted MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1200 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
50.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 1
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 30 mg: Fed MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 145 mg: Fed MSC2156119J 215 mg: Fed MSC2156119J 300 mg: Fed MSC2156119J 400 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed MSC2156119J 230 mg: Fasted
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 30 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 145 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 215 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 400 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 230 mg (capsule formulation) in the fasted state.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
51.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 2
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J 60 mg: Fed MSC2156119J 100 mg: Fed MSC2156119J 130 mg: Fed MSC2156119J 175 mg: Fed MSC2156119J 315 mg: Fed MSC2156119J 30 mg: Fasted MSC2156119J 60 mg: Fasted MSC2156119J 115 mg: Fasted MSC2156119J 115 mg: Fed
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 60 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 100 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 130 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 175 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 315 mg (capsule formulation) with food.
Subjects were administered with non-micronized MSC2156119J 30 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 60 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) in the fasted state.
Subjects were administered with non-micronized MSC2156119J 115 mg (capsule formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
52.Secondary Outcome
Title Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 3
Hide Description Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
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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.
Arm/Group Title MSC2156119J 300 mg: Fed MSC2156119J 500 mg: Fasted MSC2156119J 500 mg: Fed MSC2156119J 700 mg: Fed MSC2156119J 1000 mg: Fed MSC2156119J 1400 mg: Fed MSC2156119J 500 mg: Fed (Tablet)
Hide Arm/Group Description:
Subjects were administered with micronized MSC2156119J 300 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) in the fasted state.
Subjects were administered with micronized MSC2156119J 500 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 700 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1000 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 1400 mg (capsule formulation) with food.
Subjects were administered with micronized MSC2156119J 500 mg (tablet formulation) with food.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
53.Secondary Outcome
Title Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2
Hide Description 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.
Time Frame Baseline, Day 1 Cycle 2
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Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 17 21 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cytoplasm H-Score -12.94  (84.614) -31.43  (92.967) 5.00  (72.513)
Membrane H-Score 3.53  (123.184) 28.10  (75.407) -10.00  (75.818)
54.Secondary Outcome
Title Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2
Hide Description 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. Fold change = on-treatment value/ baseline value
Time Frame Baseline, Day 1 Cycle 2
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Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 16 17 30
Mean (Standard Deviation)
Unit of Measure: fold change
Cytoplasm H-Score (n=16, 17, 30) 1.05  (0.577) 1.09  (0.570) 1.12  (0.551)
Membrane H-Score (n= 0, 4, 5) NA [1]   (NA) 1.29  (0.934) 1.23  (0.541)
[1]
Fold change could not be calculated as there were no subjects with H-score baseline value of greater than 0.
55.Secondary Outcome
Title Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS)
Hide Description 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.
Time Frame Day 1 Cycle 2
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Hide Analysis Population Description
Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 45 62
Measure Type: Number
Unit of Measure: subjects
MMS Score 0 3 5 1
MMS Score 1 9 7 12
MMS Score 2 4 10 14
MMS Score 3 2 2 8
MMS Score Missing 24 21 27
56.Secondary Outcome
Title Relative Percentage Change In Sum of Longest Diameter (SOLD) of Target Lesions to Post-Baseline Nadir
Hide Description 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.
Time Frame Baseline, On Treatment (up to 153.3 weeks)
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Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 35 36 52
Mean (Standard Deviation)
Unit of Measure: percent change
25.67  (28.738) 16.19  (22.055) 18.87  (39.464)
57.Secondary Outcome
Title Number of Subjects With Best Overall Response (BOR)
Hide Description 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.
Time Frame Baseline up to 153.3 weeks
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Safety set included all subjects who had received at least 1 dose of MSC2156119J treatment.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 45 62
Measure Type: Number
Unit of Measure: subjects
CR 0 0 0
PR 0 0 2
SD 12 10 12
PD 25 27 38
Not evaluable 5 8 10
58.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description 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.
Time Frame Baseline up to 153.3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 41 45 62
Median (90% Confidence Interval)
Unit of Measure: months
1.4
(1.3 to 1.4)
1.3
(1.2 to 1.3)
1.4
(1.3 to 1.4)
Time Frame Baseline up to 158.01 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/42 (33.33%)   17/45 (37.78%)   22/62 (35.48%) 
Blood and lymphatic system disorders       
ANAEMIA * 1  1/42 (2.38%)  0/45 (0.00%)  1/62 (1.61%) 
LEUKOCYTOSIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Cardiac disorders       
ATRIAL FIBRILLATION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
TACHYCARDIA * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Endocrine disorders       
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Gastrointestinal disorders       
ABDOMINAL PAIN * 1  2/42 (4.76%)  1/45 (2.22%)  4/62 (6.45%) 
CONSTIPATION * 1  1/42 (2.38%)  1/45 (2.22%)  4/62 (6.45%) 
NAUSEA * 1  1/42 (2.38%)  1/45 (2.22%)  4/62 (6.45%) 
SMALL INTESTINAL OBSTRUCTION * 1  1/42 (2.38%)  4/45 (8.89%)  1/62 (1.61%) 
ASCITES * 1  0/42 (0.00%)  1/45 (2.22%)  4/62 (6.45%) 
VOMITING * 1  0/42 (0.00%)  2/45 (4.44%)  3/62 (4.84%) 
ABDOMINAL PAIN LOWER * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
FAECALOMA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
GASTROINTESTINAL HAEMORRHAGE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
IMPAIRED GASTRIC EMPTYING * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
LARGE INTESTINAL OBSTRUCTION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
MESENTERIC VEIN THROMBOSIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
General disorders       
PYREXIA * 1  1/42 (2.38%)  1/45 (2.22%)  0/62 (0.00%) 
DEVICE OCCLUSION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
DISEASE PROGRESSION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
OEDEMA PERIPHERAL * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
PAIN * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
PERIPHERAL SWELLING * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Hepatobiliary disorders       
HEPATIC FAILURE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
JAUNDICE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
JAUNDICE CHOLESTATIC * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Infections and infestations       
SEPTIC SHOCK * 1  0/42 (0.00%)  2/45 (4.44%)  0/62 (0.00%) 
STAPHYLOCOCCAL BACTERAEMIA * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
ABDOMINAL WALL INFECTION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
CELLULITIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
DEVICE RELATED INFECTION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
ESCHERICHIA URINARY TRACT INFECTION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
GANGRENE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
KIDNEY INFECTION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
LOBAR PNEUMONIA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
OSTEOMYELITIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
STAPHYLOCOCCAL INFECTION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
TRACHEOBRONCHITIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
URINARY TRACT INFECTION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
URINARY TRACT INFECTION STAPHYLOCOCCAL * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Injury, poisoning and procedural complications       
HIP FRACTURE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
SPINAL COMPRESSION FRACTURE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Investigations       
BLOOD BILIRUBIN INCREASED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
TRANSAMINASES INCREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
WAIST CIRCUMFERENCE INCREASED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Metabolism and nutrition disorders       
DEHYDRATION * 1  0/42 (0.00%)  2/45 (4.44%)  1/62 (1.61%) 
FAILURE TO THRIVE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
HYPERKALAEMIA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Musculoskeletal and connective tissue disorders       
MUSCULAR WEAKNESS * 1  1/42 (2.38%)  1/45 (2.22%)  1/62 (1.61%) 
MUSCULOSKELETAL CHEST PAIN * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
OSTEONECROSIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
METASTASES TO CENTRAL NERVOUS SYSTEM * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
TUMOUR HAEMORRHAGE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Nervous system disorders       
HEADACHE * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
SPINAL CORD COMPRESSION * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
SYNCOPE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
VAGUS NERVE DISORDER * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Psychiatric disorders       
MENTAL STATUS CHANGES * 1  0/42 (0.00%)  0/45 (0.00%)  3/62 (4.84%) 
Renal and urinary disorders       
ACUTE KIDNEY INJURY * 1  0/42 (0.00%)  2/45 (4.44%)  0/62 (0.00%) 
HYDRONEPHROSIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
URINARY INCONTINENCE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Reproductive system and breast disorders       
VAGINAL HAEMORRHAGE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
PLEURAL EFFUSION * 1  2/42 (4.76%)  1/45 (2.22%)  1/62 (1.61%) 
PULMONARY EMBOLISM * 1  2/42 (4.76%)  2/45 (4.44%)  0/62 (0.00%) 
DYSPNOEA * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
PNEUMONIA ASPIRATION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Vascular disorders       
JUGULAR VEIN THROMBOSIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
SUPERIOR VENA CAVA SYNDROME * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MSC2156119J Regimen 1 MSC2156119J Regimen 2 MSC2156119J Regimen 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   41/42 (97.62%)   45/45 (100.00%)   59/62 (95.16%) 
Blood and lymphatic system disorders       
ANAEMIA * 1  4/42 (9.52%)  4/45 (8.89%)  7/62 (11.29%) 
LEUKOCYTOSIS * 1  2/42 (4.76%)  5/45 (11.11%)  2/62 (3.23%) 
THROMBOCYTOPENIA * 1  4/42 (9.52%)  2/45 (4.44%)  2/62 (3.23%) 
NEUTROPENIA * 1  0/42 (0.00%)  3/45 (6.67%)  2/62 (3.23%) 
LEUKOPENIA * 1  2/42 (4.76%)  1/45 (2.22%)  1/62 (1.61%) 
ANAEMIA OF CHRONIC DISEASE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
HAEMOLYTIC ANAEMIA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
HAEMORRHAGIC ANAEMIA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
THROMBOCYTOSIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Cardiac disorders       
TACHYCARDIA * 1  2/42 (4.76%)  2/45 (4.44%)  5/62 (8.06%) 
ATRIAL FIBRILLATION * 1  1/42 (2.38%)  1/45 (2.22%)  0/62 (0.00%) 
ANGINA PECTORIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
BRADYCARDIA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
SINUS ARRHYTHMIA * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Ear and labyrinth disorders       
DEAFNESS * 1  1/42 (2.38%)  0/45 (0.00%)  1/62 (1.61%) 
EAR DISCOMFORT * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
EAR PAIN * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
EAR SWELLING * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
MIDDLE EAR EFFUSION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
VERTIGO * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
VERTIGO POSITIONAL * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
Endocrine disorders       
HYPOTHYROIDISM * 1  2/42 (4.76%)  1/45 (2.22%)  1/62 (1.61%) 
BASEDOW'S DISEASE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
THYROID DISORDER * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Eye disorders       
VISION BLURRED * 1  2/42 (4.76%)  0/45 (0.00%)  4/62 (6.45%) 
DRY EYE * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
LACRIMATION INCREASED * 1  1/42 (2.38%)  0/45 (0.00%)  1/62 (1.61%) 
BLEPHAROSPASM * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
RETINAL PIGMENT EPITHELIOPATHY * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
VISUAL ACUITY REDUCED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
VITREOUS FLOATERS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Gastrointestinal disorders       
CONSTIPATION * 1  12/42 (28.57%)  10/45 (22.22%)  16/62 (25.81%) 
NAUSEA * 1  11/42 (26.19%)  10/45 (22.22%)  11/62 (17.74%) 
VOMITING * 1  11/42 (26.19%)  8/45 (17.78%)  10/62 (16.13%) 
ABDOMINAL PAIN * 1  4/42 (9.52%)  7/45 (15.56%)  9/62 (14.52%) 
DIARRHOEA * 1  7/42 (16.67%)  6/45 (13.33%)  6/62 (9.68%) 
ABDOMINAL DISTENSION * 1  2/42 (4.76%)  5/45 (11.11%)  6/62 (9.68%) 
ASCITES * 1  1/42 (2.38%)  6/45 (13.33%)  6/62 (9.68%) 
DRY MOUTH * 1  2/42 (4.76%)  2/45 (4.44%)  5/62 (8.06%) 
ABDOMINAL PAIN UPPER * 1  0/42 (0.00%)  3/45 (6.67%)  2/62 (3.23%) 
DYSPHAGIA * 1  1/42 (2.38%)  1/45 (2.22%)  3/62 (4.84%) 
GASTROOESOPHAGEAL REFLUX DISEASE * 1  4/42 (9.52%)  1/45 (2.22%)  0/62 (0.00%) 
HAEMORRHOIDS * 1  1/42 (2.38%)  1/45 (2.22%)  1/62 (1.61%) 
ABDOMINAL PAIN LOWER * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
DYSPEPSIA * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
MELAENA * 1  2/42 (4.76%)  0/45 (0.00%)  0/62 (0.00%) 
STOMATITIS * 1  0/42 (0.00%)  2/45 (4.44%)  0/62 (0.00%) 
ABDOMINAL DISCOMFORT * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
ABDOMINAL MASS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
CHANGE OF BOWEL HABIT * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
ERUCTATION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
FAECAL INCONTINENCE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
FAECES DISCOLOURED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
FLATULENCE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
GASTROINTESTINAL HAEMORRHAGE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
GASTROINTESTINAL MOTILITY DISORDER * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
GASTROINTESTINAL SOUNDS ABNORMAL * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
GINGIVAL PAIN * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
HAEMATOCHEZIA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
LIP SWELLING * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
NEUROGENIC BOWEL * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
ODYNOPHAGIA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
RETCHING * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
TOOTHACHE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
General disorders       
FATIGUE * 1  12/42 (28.57%)  17/45 (37.78%)  20/62 (32.26%) 
OEDEMA PERIPHERAL * 1  6/42 (14.29%)  9/45 (20.00%)  24/62 (38.71%) 
PYREXIA * 1  5/42 (11.90%)  1/45 (2.22%)  6/62 (9.68%) 
CHILLS * 1  2/42 (4.76%)  1/45 (2.22%)  4/62 (6.45%) 
NON-CARDIAC CHEST PAIN * 1  1/42 (2.38%)  4/45 (8.89%)  1/62 (1.61%) 
MALAISE * 1  0/42 (0.00%)  3/45 (6.67%)  1/62 (1.61%) 
PERIPHERAL SWELLING * 1  3/42 (7.14%)  0/45 (0.00%)  1/62 (1.61%) 
ASTHENIA * 1  1/42 (2.38%)  1/45 (2.22%)  1/62 (1.61%) 
AXILLARY PAIN * 1  1/42 (2.38%)  0/45 (0.00%)  1/62 (1.61%) 
EARLY SATIETY * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
GAIT DISTURBANCE * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
LOCAL SWELLING * 1  1/42 (2.38%)  1/45 (2.22%)  0/62 (0.00%) 
OEDEMA * 1  0/42 (0.00%)  1/45 (2.22%)  1/62 (1.61%) 
PAIN * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
CATHETER SITE ERYTHEMA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
FEELING COLD * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
GENERALISED OEDEMA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
LOCALISED OEDEMA * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
SENSATION OF FOREIGN BODY * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Hepatobiliary disorders       
HYPERBILIRUBINAEMIA * 1  0/42 (0.00%)  5/45 (11.11%)  0/62 (0.00%) 
JAUNDICE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
PORTAL VEIN THROMBOSIS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Immune system disorders       
ALLERGY TO ARTHROPOD BITE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Infections and infestations       
URINARY TRACT INFECTION * 1  2/42 (4.76%)  3/45 (6.67%)  7/62 (11.29%) 
ORAL CANDIDIASIS * 1  1/42 (2.38%)  4/45 (8.89%)  2/62 (3.23%) 
PNEUMONIA * 1  0/42 (0.00%)  1/45 (2.22%)  3/62 (4.84%) 
SINUSITIS * 1  1/42 (2.38%)  2/45 (4.44%)  1/62 (1.61%) 
FUNGAL INFECTION * 1  0/42 (0.00%)  2/45 (4.44%)  1/62 (1.61%) 
UPPER RESPIRATORY TRACT INFECTION * 1  2/42 (4.76%)  0/45 (0.00%)  1/62 (1.61%) 
STAPHYLOCOCCAL INFECTION * 1  1/42 (2.38%)  1/45 (2.22%)  0/62 (0.00%) 
BRONCHITIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
CELLULITIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
CONJUNCTIVITIS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
DEVICE RELATED INFECTION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
EAR INFECTION * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
HORDEOLUM * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
INFECTED FISTULA * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
NAIL BED INFECTION FUNGAL * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
ONYCHOMYCOSIS * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
PAROTITIS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
POST PROCEDURAL INFECTION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
TOOTH ABSCESS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
UPPER RESPIRATORY TRACT INFECTION BACTERIAL * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
UROSEPSIS * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
WOUND INFECTION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
Injury, poisoning and procedural complications       
FALL * 1  0/42 (0.00%)  3/45 (6.67%)  1/62 (1.61%) 
ANKLE FRACTURE * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
CONTUSION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
EPICONDYLITIS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
FEEDING TUBE COMPLICATION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
JOINT INJURY * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
LACERATION * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
LIMB INJURY * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
NAIL INJURY * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
PROCEDURAL HAEMORRHAGE * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
RADIATION PNEUMONITIS * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
SPINAL COMPRESSION FRACTURE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
STOMA SITE HAEMORRHAGE * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
Investigations       
ASPARTATE AMINOTRANSFERASE INCREASED * 1  7/42 (16.67%)  5/45 (11.11%)  8/62 (12.90%) 
LIPASE INCREASED * 1  3/42 (7.14%)  4/45 (8.89%)  2/62 (3.23%) 
TRANSAMINASES INCREASED * 1  1/42 (2.38%)  1/45 (2.22%)  7/62 (11.29%) 
ALANINE AMINOTRANSFERASE INCREASED * 1  1/42 (2.38%)  1/45 (2.22%)  6/62 (9.68%) 
BLOOD CREATININE INCREASED * 1  3/42 (7.14%)  0/45 (0.00%)  5/62 (8.06%) 
BLOOD BILIRUBIN INCREASED * 1  1/42 (2.38%)  3/45 (6.67%)  2/62 (3.23%) 
BREATH SOUNDS ABNORMAL * 1  2/42 (4.76%)  1/45 (2.22%)  3/62 (4.84%) 
WEIGHT DECREASED * 1  0/42 (0.00%)  1/45 (2.22%)  3/62 (4.84%) 
AMYLASE INCREASED * 1  2/42 (4.76%)  1/45 (2.22%)  0/62 (0.00%) 
BLOOD ALKALINE PHOSPHATASE INCREASED * 1  1/42 (2.38%)  0/45 (0.00%)  1/62 (1.61%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
HAEMOGLOBIN INCREASED * 1  0/42 (0.00%)  2/45 (4.44%)  0/62 (0.00%) 
INTERNATIONAL NORMALISED RATIO INCREASED * 1  0/42 (0.00%)  2/45 (4.44%)  0/62 (0.00%) 
PROSTATIC SPECIFIC ANTIGEN INCREASED * 1  0/42 (0.00%)  0/45 (0.00%)  2/62 (3.23%) 
WEIGHT INCREASED * 1  1/42 (2.38%)  1/45 (2.22%)  0/62 (0.00%) 
ANTICOAGULATION DRUG LEVEL BELOW THERAPEUTIC * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
BLOOD CREATINE INCREASED * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
BLOOD GLUCOSE DECREASED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
BLOOD GLUCOSE INCREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
BLOOD LACTATE DEHYDROGENASE INCREASED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
BLOOD PRESSURE DIASTOLIC ABNORMAL * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
BLOOD UREA INCREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
ELECTROCARDIOGRAM PR SHORTENED * 1  1/42 (2.38%)  0/45 (0.00%)  0/62 (0.00%) 
ELECTROCARDIOGRAM QT PROLONGED * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
ELECTROCARDIOGRAM ST SEGMENT ELEVATION * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
HAEMATOCRIT INCREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
NEUTROPHIL COUNT INCREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
PEDAL PULSE ABNORMAL * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
PLATELET COUNT DECREASED * 1  0/42 (0.00%)  1/45 (2.22%)  0/62 (0.00%) 
WAIST CIRCUMFERENCE INCREASED * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
WHITE BLOOD CELL COUNT INCREASED * 1  0/42 (0.00%)  0/45 (0.00%)  1/62 (1.61%) 
HYPOKALAEMIA * 1  3/42 (7.14%)  3/45 (6.67%)  2/62 (3.23%) 
Metabolism and nutrition disorders       
DECREASED APPETITE * 1  12/42 (28.57%)  5/45 (11.11%)  27/62 (43.55%) 
HYPOALBUMINAEMIA * 1  8/42 (19.05%)  6/45 (13.33%)  11/62 (17.74%) 
DEHYDRATION * 1  2/42 (4.76%)  4/45 (8.89%)  9/62 (14.52%) 
HYPONATRAEMIA * 1  3/42 (7.14%)  2/45 (4.44%)  8/62 (12.90%) 
HYPOMAGNESAEMIA * 1  4/42 (9.52%)