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

• Sponsor: EMD Serono (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01014936
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 149
• Location: 1
• Arms: 3
• Actual Duration (Months): 71
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore MSC2156119J, in subjects with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available.

Subjects will be assigned one of the dosing regimens:

• Regimen 1: MSC2156119J once daily for 14 days, followed by 7 days with no treatment (21-day cycle)

• Regimen 2: MSC2156119J three times per week (e.g., Days 1, 3, and 5) for three weeks (21-day cycle)

• Regimen 3: MSC2156119J every day for three weeks (21-day cycle)

Condition or Disease	Intervention/Treatment	Phase
Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available	Drug: MSC2156119J	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor MSC2156119J Under Three Different Regimens in Subjects With Advanced Solid Tumors
• Actual Study Start Date: Nov 30, 2009
• Actual Primary Completion Date: Oct 31, 2015
• Actual Study Completion Date: Oct 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MSC2156119J Regimen 1 Subjects will be 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.	Drug: MSC2156119J; Other Names: EMD 1214063 Tepotinib
Experimental: MSC2156119J Regimen 2 Subjects will be 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.	Drug: MSC2156119J; Other Names: EMD 1214063 Tepotinib
Experimental: MSC2156119J Regimen 3 Subjects will be 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.	Drug: MSC2156119J; Other Names: EMD 1214063 Tepotinib

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Any Dose Limiting Toxicity (DLT) [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)]

   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.

2. Recommended Phase 2 Dose (RP2D) [Cycle 1 (Day 1 to Day 21)]

   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.

3. Number of Subjects With Treatment-Related Adverse Events [Baseline up to 158.01 weeks]

   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.

Secondary Outcome Measures

1. Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death [Baseline up to 158.01 weeks]

   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.

2. Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

3. Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

4. Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

5. Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

6. Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

7. Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

8. Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

9. Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1]

10. Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

11. Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

12. Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

13. Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

14. Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

15. Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

16. Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

17. Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

18. Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

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

19. Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

20. Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

    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.

21. 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 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

    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.

22. 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 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

    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.

23. 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 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

    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.

24. 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 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

    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.

25. 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 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

    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".

26. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

27. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

28. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

29. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

30. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1]

31. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

32. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

33. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1]

34. Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

35. Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

36. Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

37. Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

38. Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

39. Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

40. Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

41. Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

42. Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

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

43. Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

44. Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

45. Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

46. Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1]

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

47. Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 1 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

48. Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 2 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1]

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

49. Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 3 [pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1]

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

50. Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 [Baseline, Day 1 Cycle 2]

    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.

51. Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 [Baseline, Day 1 Cycle 2]

    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

52. Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) [Day 1 Cycle 2]

    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.

53. Relative Percentage Change In Sum of Longest Diameter (SOLD) of Target Lesions to Post-Baseline Nadir [Baseline, On Treatment (up to 153.3 weeks)]

    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.

54. Number of Subjects With Best Overall Response (BOR) [Baseline up to 153.3 weeks]

    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.

55. Progression-free Survival (PFS) [Baseline up to 153.3 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject should read and fully understand the requirements of the trial, be willing to comply with all trial visits and assessments, and be willing and able to give informed consent

2. Histologically or cytologically confirmed solid tumor, either refractory to standard therapy or for which no effective standard therapy is available

3. Measurable or evaluable disease, as defined by RECIST 1.0

4. Estimated life expectancy greater than (>) three months

5. Men or women aged greater than or equal to (>=) 18 years

6. Women of childbearing potential must have a negative blood pregnancy test at the Screening Visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are post-menopausal for at least 12 months, are surgically sterile, or are sexually inactive.

7. Subjects and their partners must be willing to avoid pregnancy during the trial and until three months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicide or intrauterine device. This requirement begins two weeks before receiving the first trial treatment and ends one month after receiving the last treatment.

8. ECOG performance status of 0 to 2

9. Adequate hematological function:

• Hemoglobin >= 9.0 g/dL

• Neutrophils > 1.5 x 109/L

• Platelets >= 75 x 109/L

1. Adequate liver function:

• Total bilirubin less than or equal to (<=) 1.5 x ULN (upper limit to normal)

• AST/ ALT ≤ 2.5 x ULN

For subjects with liver metastases:

• Total bilirubin ≤ 1.5 x ULN

• AST/ ALT ≤ 5 x ULN

1. Adequate renal function:

• Serum creatinine < 1.5 x ULN, and/or

• Calculated creatinine clearance > 60 mL/min

1. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade <= 2, except for alopecia

2. Recovery from any surgical intervention

3. Subjects enrolling after the MTD has been determined must present specific c Met alterations (mutation, overexpression, amplification

Exclusion Criteria:

1. Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)

2. Received extensive prior radiotherapy on more than 30% of bone marrow

3. Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids

4. Known HIV positivity, active hepatitis C, or active hepatitis B

5. Medical history of liver fibrosis/ cirrhosis

6. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such

7. Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product

8. Medical history of surgery within six weeks prior to enrollment

9. Impaired cardiac function (left ventricular ejection fraction < 45% defined by echocardiograph, serious arrhythmia, unstable angina pectoris, congestive heart failure NYHA III and IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion)

10. Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mm Hg)

11. Peripheral neuropathy Grade >= 2

12. Medical history of any other significant medical disease, major surgery, or psychiatric condition that might impair the subject's well being or preclude full participation in the trial

13. Women who are pregnant or nursing

14. Known drug abuse or alcohol abuse

15. Participation in another clinical trial within the past 28 days

16. Requires concurrent treatment with a non-permitted drug

17. Known hypersensitivity to any of the trial treatment ingredients

18. Legal incapacity or limited legal capacity

19. Any other reason that, in the opinion of the principal investigator, precludes the subject from participating in the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M.D. Anderson Cancer Center	Houston	Texas	United States

Sponsors and Collaborators

• EMD Serono
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)

Publications

None provided.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT01014936
• Other Study ID Numbers: EMR200095_001; 2013-003767-63
• First Posted: Nov 17, 2009
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• Keywords provided by EMD Serono: Phase 1; advanced solid tumors; refractory to standard therapy
• Additional relevant MeSH terms: Neoplasms; Tepotinib

Study Results

Participant Flow

Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	MSC2156119J Regimen 1	MSC2156119J Regimen 2	MSC2156119J Regimen 3	Total
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 Participants	42	45	62	149
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.97 (13.496)	59.29 (14.656)	56.49 (13.986)	58.32 (14.050)
Sex: Female, Male (Count of 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%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Any Dose Limiting Toxicity (DLT)
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)

Outcome Measure Data

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
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.
Measure Participants	42	42	21
Number [subjects]	1	3	2

2. Primary Outcome

Title	Recommended Phase 2 Dose (RP2D)
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)

Outcome Measure Data

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
Arm/Group Description	All subjects who were administered with micronized or non-micronized MSC2156119J (capsule or tablet formulation) in any of the three regimens.
Measure Participants	105
Number [milligram]	500

3. Primary Outcome

Title	Number of Subjects With Treatment-Related Adverse Events
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

Outcome Measure Data

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
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.
Measure Participants	42	45	62
Number [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
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

Outcome Measure Data

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
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.
Measure Participants	42	45	62
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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	3	3	3	3	3	3	3	3	3	6	6	3
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	6	6	6	3	4	3	4	6	7
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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)
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.
Measure Participants	3	1	19	3	7	1	6	22
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	246.5 (32.7)	552.0 (NA)	329.9 (72.4)	433.5 (27.6)	666.1 (46.0)	761.0 (NA)	863.4 (37.4)	460.9 (58.7)

8. Secondary Outcome

Title	Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	2	3	3	3	3	3	3	3	3	6	3	3
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	5	5	6	3	3	3	3	6	6
Geometric Mean (Geometric Coefficient of Variation) [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
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

Outcome Measure Data

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)
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.
Measure Participants	3	1	17	3	6	4	18
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	741.6 (45.7)	795.0 (NA)	943.1 (34.6)	1006 (39.4)	1219 (59.2)	1805 (31.2)	1291 (48.1)

11. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	3	3	3	3	3	3	3	3	3	6	6	3
Median (Full Range) [hours]	8.000	10.000	10.000	8.000	8.000	10.000	8.000	4.000	8.000	10.000	24.000	8.000

12. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	6	6	6	3	4	3	4	6	7
Median (Full Range) [hours]	9.000	8.000	9.000	8.000	24.000	10.000	17.042	33.083	24.000

13. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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)
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.
Measure Participants	3	1	19	3	7	1	6	22
Median (Full Range) [hours]	8.000	8.000	10.000	10.000	10.000	10.000	24.000	8.025

14. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	2	3	3	3	3	3	3	3	3	6	3	3
Median (Full Range) [hours]	2.125	8.000	8.000	4.000	8.000	8.000	0.250	4.000	4.000	6.000	0.00	4.000

15. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	5	5	6	3	3	3	3	6	6
Median (Full Range) [hours]	10.000	10.000	8.000	10.000	8.000	8.000	8.067	17.083	10.000

16. Secondary Outcome

Title	Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	3	1	17	3	6	4	18
Median (Full Range) [hours]	10.000	10.000	8.000	3.183	8.833	9.075	8.000

17. Secondary Outcome

Title	Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

18. Secondary Outcome

Title	Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

19. Secondary Outcome

Title	Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0	0

20. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

21. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

22. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0

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
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

Outcome Measure Data

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
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.
Measure Participants	3	3	3	3	3	3	3	3	3	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [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
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

Outcome Measure Data

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
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.
Measure Participants	6	6	6	3	4	3	4	6	7
Geometric Mean (Geometric Coefficient of Variation) [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
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

Outcome Measure Data

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)
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.
Measure Participants	3	1	19	3	7	1	6	22
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	4209.3 (33.4)	3190.8 (NA)	5667.3 (76.1)	4980.9 (86.3)	10355.6 (59.6)	13352.6 (NA)	15542.0 (41.9)	7661.8 (66.7)

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
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

Outcome Measure Data

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
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.
Measure Participants	2	3	3	3	3	3	3	3	3	6	3	3
Geometric Mean (Geometric Coefficient of Variation) [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
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

Outcome Measure Data

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
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.
Measure Participants	5	5	6	3	3	3	3	6	6
Geometric Mean (Geometric Coefficient of Variation) [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
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

Outcome Measure Data

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)
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.
Measure Participants	3	1	17	3	6	4	18
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	15694.9 (50.8)	17498.1 (NA)	20210.4 (33.5)	17107.8 (3.2)	27716.9 (58.6)	39730.6 (29.5)	18915.7 (87.5)

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
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

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
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

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
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0	0

32. Secondary Outcome

Title	Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	3	3	2	3	3	3	3	2	3	5	6	3
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	6	6	6	3	4	3	3	4	7
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

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)
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.
Measure Participants	3	1	18	2	6	1	6	22
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	4206.5 (33.5)	NA (NA)	5917.9 (74.8)	7575.8 (24.6)	11796.4 (48.1)	NA (NA)	15542.0 (41.9)	7637.3 (66.7)

35. Secondary Outcome

Title	Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	2	3	3	3	3	3	3	3	3	6	3	3
Geometric Mean (Geometric Coefficient of Variation) [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
Time Frame	pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1

Outcome Measure Data

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
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.
Measure Participants	5	4	5	1	3	2	3	5	4
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	3031.7 (55.8)	7565.6 (35.0)	5305.5 (62.6)	9051.1 (NA)	27760.2 (25.1)	273.7 (909.0)	2054.1 (33.3)	1634.4 (103.5)	3538.9 (64.9)

37. Secondary Outcome

Title	Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	3	1	17	3	6	4	13
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	15597.6 (50.0)	17498.1 (NA)	20169.3 (33.5)	21972.2 (42.9)	27214.4 (59.4)	39283.7 (28.0)	27437.7 (51.7)

38. Secondary Outcome

Title	Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

39. Secondary Outcome

Title	Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

40. Secondary Outcome

Title	Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0	0

41. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

42. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

43. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0	0

44. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

45. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

46. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0

47. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

48. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

49. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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)
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.
Measure Participants	0	0	0	0	0	0	0	0

50. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 1
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0

51. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 2
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

Outcome Measure Data

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
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.
Measure Participants	0	0	0	0	0	0	0	0	0

52. Secondary Outcome

Title	Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 3
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

Outcome Measure Data

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 1400 mg: Fed	MSC2156119J 500 mg: Fed (Tablet)
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.
Measure Participants	0	0	0	0	0	0	0

53. Secondary Outcome

Title	Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2
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

Outcome Measure Data

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
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.
Measure Participants	17	21	32
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
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

Outcome Measure Data

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
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.
Measure Participants	16	17	30
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 (NA)	1.29 (0.934)	1.23 (0.541)

55. Secondary Outcome

Title	Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS)
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

Outcome Measure Data

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
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.
Measure Participants	42	45	62
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
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)

Outcome Measure Data

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
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.
Measure Participants	35	36	52
Mean (Standard Deviation) [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)
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

Outcome Measure Data

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
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.
Measure Participants	42	45	62
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)
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

Outcome Measure Data

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
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.
Measure Participants	41	45	62
Median (90% Confidence Interval) [months]	1.4	1.3	1.4

Adverse Events

Time Frame	Baseline up to 158.01 weeks
Arm/Group Title	MSC2156119J Regimen 1		MSC2156119J Regimen 2		MSC2156119J Regimen 3
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MSC2156119J Regimen 1		MSC2156119J Regimen 2		MSC2156119J Regimen 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/42 (33.3%)		17/45 (37.8%)		22/62 (35.5%)
Blood and lymphatic system disorders
ANAEMIA	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
LEUKOCYTOSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Cardiac disorders
ATRIAL FIBRILLATION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
TACHYCARDIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Endocrine disorders
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Gastrointestinal disorders
ABDOMINAL PAIN	2/42 (4.8%)		1/45 (2.2%)		4/62 (6.5%)
CONSTIPATION	1/42 (2.4%)		1/45 (2.2%)		4/62 (6.5%)
NAUSEA	1/42 (2.4%)		1/45 (2.2%)		4/62 (6.5%)
SMALL INTESTINAL OBSTRUCTION	1/42 (2.4%)		4/45 (8.9%)		1/62 (1.6%)
ASCITES	0/42 (0%)		1/45 (2.2%)		4/62 (6.5%)
VOMITING	0/42 (0%)		2/45 (4.4%)		3/62 (4.8%)
ABDOMINAL PAIN LOWER	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
FAECALOMA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
GASTROINTESTINAL HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
IMPAIRED GASTRIC EMPTYING	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
LARGE INTESTINAL OBSTRUCTION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
MESENTERIC VEIN THROMBOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
General disorders
PYREXIA	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
DEVICE OCCLUSION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
DISEASE PROGRESSION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
OEDEMA PERIPHERAL	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
PAIN	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
PERIPHERAL SWELLING	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Hepatobiliary disorders
HEPATIC FAILURE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
JAUNDICE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
JAUNDICE CHOLESTATIC	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Infections and infestations
SEPTIC SHOCK	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
STAPHYLOCOCCAL BACTERAEMIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
ABDOMINAL WALL INFECTION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
CELLULITIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
DEVICE RELATED INFECTION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
ESCHERICHIA URINARY TRACT INFECTION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
GANGRENE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
KIDNEY INFECTION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
LOBAR PNEUMONIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
OSTEOMYELITIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
STAPHYLOCOCCAL INFECTION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
TRACHEOBRONCHITIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
URINARY TRACT INFECTION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
URINARY TRACT INFECTION STAPHYLOCOCCAL	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Injury, poisoning and procedural complications
HIP FRACTURE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
SPINAL COMPRESSION FRACTURE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Investigations
BLOOD BILIRUBIN INCREASED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
TRANSAMINASES INCREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
WAIST CIRCUMFERENCE INCREASED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Metabolism and nutrition disorders
DEHYDRATION	0/42 (0%)		2/45 (4.4%)		1/62 (1.6%)
FAILURE TO THRIVE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HYPERKALAEMIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
MUSCULOSKELETAL CHEST PAIN	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
OSTEONECROSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
TUMOUR HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Nervous system disorders
HEADACHE	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
SPINAL CORD COMPRESSION	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
SYNCOPE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
VAGUS NERVE DISORDER	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Psychiatric disorders
MENTAL STATUS CHANGES	0/42 (0%)		0/45 (0%)		3/62 (4.8%)
Renal and urinary disorders
ACUTE KIDNEY INJURY	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
HYDRONEPHROSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
URINARY INCONTINENCE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION	2/42 (4.8%)		1/45 (2.2%)		1/62 (1.6%)
PULMONARY EMBOLISM	2/42 (4.8%)		2/45 (4.4%)		0/62 (0%)
DYSPNOEA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
PNEUMONIA ASPIRATION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Vascular disorders
JUGULAR VEIN THROMBOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
SUPERIOR VENA CAVA SYNDROME	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	MSC2156119J Regimen 1		MSC2156119J Regimen 2		MSC2156119J Regimen 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/42 (97.6%)		45/45 (100%)		59/62 (95.2%)
Blood and lymphatic system disorders
ANAEMIA	4/42 (9.5%)		4/45 (8.9%)		7/62 (11.3%)
LEUKOCYTOSIS	2/42 (4.8%)		5/45 (11.1%)		2/62 (3.2%)
THROMBOCYTOPENIA	4/42 (9.5%)		2/45 (4.4%)		2/62 (3.2%)
NEUTROPENIA	0/42 (0%)		3/45 (6.7%)		2/62 (3.2%)
LEUKOPENIA	2/42 (4.8%)		1/45 (2.2%)		1/62 (1.6%)
ANAEMIA OF CHRONIC DISEASE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HAEMOLYTIC ANAEMIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
HAEMORRHAGIC ANAEMIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
THROMBOCYTOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Cardiac disorders
TACHYCARDIA	2/42 (4.8%)		2/45 (4.4%)		5/62 (8.1%)
ATRIAL FIBRILLATION	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
ANGINA PECTORIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BRADYCARDIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SINUS ARRHYTHMIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Ear and labyrinth disorders
DEAFNESS	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
EAR DISCOMFORT	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
EAR PAIN	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
EAR SWELLING	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
MIDDLE EAR EFFUSION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
VERTIGO	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
VERTIGO POSITIONAL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Endocrine disorders
HYPOTHYROIDISM	2/42 (4.8%)		1/45 (2.2%)		1/62 (1.6%)
BASEDOW'S DISEASE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
THYROID DISORDER	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Eye disorders
VISION BLURRED	2/42 (4.8%)		0/45 (0%)		4/62 (6.5%)
DRY EYE	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
LACRIMATION INCREASED	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
BLEPHAROSPASM	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
RETINAL PIGMENT EPITHELIOPATHY	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
VISUAL ACUITY REDUCED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
VITREOUS FLOATERS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Gastrointestinal disorders
CONSTIPATION	12/42 (28.6%)		10/45 (22.2%)		16/62 (25.8%)
NAUSEA	11/42 (26.2%)		10/45 (22.2%)		11/62 (17.7%)
VOMITING	11/42 (26.2%)		8/45 (17.8%)		10/62 (16.1%)
ABDOMINAL PAIN	4/42 (9.5%)		7/45 (15.6%)		9/62 (14.5%)
DIARRHOEA	7/42 (16.7%)		6/45 (13.3%)		6/62 (9.7%)
ABDOMINAL DISTENSION	2/42 (4.8%)		5/45 (11.1%)		6/62 (9.7%)
ASCITES	1/42 (2.4%)		6/45 (13.3%)		6/62 (9.7%)
DRY MOUTH	2/42 (4.8%)		2/45 (4.4%)		5/62 (8.1%)
ABDOMINAL PAIN UPPER	0/42 (0%)		3/45 (6.7%)		2/62 (3.2%)
DYSPHAGIA	1/42 (2.4%)		1/45 (2.2%)		3/62 (4.8%)
GASTROOESOPHAGEAL REFLUX DISEASE	4/42 (9.5%)		1/45 (2.2%)		0/62 (0%)
HAEMORRHOIDS	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
ABDOMINAL PAIN LOWER	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
DYSPEPSIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
MELAENA	2/42 (4.8%)		0/45 (0%)		0/62 (0%)
STOMATITIS	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
ABDOMINAL DISCOMFORT	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ABDOMINAL MASS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
CHANGE OF BOWEL HABIT	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ERUCTATION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
FAECAL INCONTINENCE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
FAECES DISCOLOURED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
FLATULENCE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
GASTROINTESTINAL HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
GASTROINTESTINAL MOTILITY DISORDER	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
GASTROINTESTINAL SOUNDS ABNORMAL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
GINGIVAL PAIN	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
HAEMATOCHEZIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
LIP SWELLING	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
NEUROGENIC BOWEL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ODYNOPHAGIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RETCHING	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
TOOTHACHE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
General disorders
FATIGUE	12/42 (28.6%)		17/45 (37.8%)		20/62 (32.3%)
OEDEMA PERIPHERAL	6/42 (14.3%)		9/45 (20%)		24/62 (38.7%)
PYREXIA	5/42 (11.9%)		1/45 (2.2%)		6/62 (9.7%)
CHILLS	2/42 (4.8%)		1/45 (2.2%)		4/62 (6.5%)
NON-CARDIAC CHEST PAIN	1/42 (2.4%)		4/45 (8.9%)		1/62 (1.6%)
MALAISE	0/42 (0%)		3/45 (6.7%)		1/62 (1.6%)
PERIPHERAL SWELLING	3/42 (7.1%)		0/45 (0%)		1/62 (1.6%)
ASTHENIA	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
AXILLARY PAIN	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
EARLY SATIETY	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
GAIT DISTURBANCE	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
LOCAL SWELLING	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
OEDEMA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
PAIN	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
CATHETER SITE ERYTHEMA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
FEELING COLD	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
GENERALISED OEDEMA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
LOCALISED OEDEMA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SENSATION OF FOREIGN BODY	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	0/42 (0%)		5/45 (11.1%)		0/62 (0%)
JAUNDICE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
PORTAL VEIN THROMBOSIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Immune system disorders
ALLERGY TO ARTHROPOD BITE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Infections and infestations
URINARY TRACT INFECTION	2/42 (4.8%)		3/45 (6.7%)		7/62 (11.3%)
ORAL CANDIDIASIS	1/42 (2.4%)		4/45 (8.9%)		2/62 (3.2%)
PNEUMONIA	0/42 (0%)		1/45 (2.2%)		3/62 (4.8%)
SINUSITIS	1/42 (2.4%)		2/45 (4.4%)		1/62 (1.6%)
FUNGAL INFECTION	0/42 (0%)		2/45 (4.4%)		1/62 (1.6%)
UPPER RESPIRATORY TRACT INFECTION	2/42 (4.8%)		0/45 (0%)		1/62 (1.6%)
STAPHYLOCOCCAL INFECTION	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
BRONCHITIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
CELLULITIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
CONJUNCTIVITIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
DEVICE RELATED INFECTION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
EAR INFECTION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
HORDEOLUM	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
INFECTED FISTULA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
NAIL BED INFECTION FUNGAL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ONYCHOMYCOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
PAROTITIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
POST PROCEDURAL INFECTION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
TOOTH ABSCESS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
UPPER RESPIRATORY TRACT INFECTION BACTERIAL	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
UROSEPSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
WOUND INFECTION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Injury, poisoning and procedural complications
FALL	0/42 (0%)		3/45 (6.7%)		1/62 (1.6%)
ANKLE FRACTURE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
CONTUSION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
EPICONDYLITIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
FEEDING TUBE COMPLICATION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
JOINT INJURY	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
LACERATION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
LIMB INJURY	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
NAIL INJURY	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
PROCEDURAL HAEMORRHAGE	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RADIATION PNEUMONITIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SPINAL COMPRESSION FRACTURE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
STOMA SITE HAEMORRHAGE	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED	7/42 (16.7%)		5/45 (11.1%)		8/62 (12.9%)
LIPASE INCREASED	3/42 (7.1%)		4/45 (8.9%)		2/62 (3.2%)
TRANSAMINASES INCREASED	1/42 (2.4%)		1/45 (2.2%)		7/62 (11.3%)
ALANINE AMINOTRANSFERASE INCREASED	1/42 (2.4%)		1/45 (2.2%)		6/62 (9.7%)
BLOOD CREATININE INCREASED	3/42 (7.1%)		0/45 (0%)		5/62 (8.1%)
BLOOD BILIRUBIN INCREASED	1/42 (2.4%)		3/45 (6.7%)		2/62 (3.2%)
BREATH SOUNDS ABNORMAL	2/42 (4.8%)		1/45 (2.2%)		3/62 (4.8%)
WEIGHT DECREASED	0/42 (0%)		1/45 (2.2%)		3/62 (4.8%)
AMYLASE INCREASED	2/42 (4.8%)		1/45 (2.2%)		0/62 (0%)
BLOOD ALKALINE PHOSPHATASE INCREASED	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
HAEMOGLOBIN INCREASED	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
INTERNATIONAL NORMALISED RATIO INCREASED	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
PROSTATIC SPECIFIC ANTIGEN INCREASED	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
WEIGHT INCREASED	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
ANTICOAGULATION DRUG LEVEL BELOW THERAPEUTIC	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BLOOD CREATINE INCREASED	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
BLOOD GLUCOSE DECREASED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BLOOD GLUCOSE INCREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
BLOOD LACTATE DEHYDROGENASE INCREASED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BLOOD PRESSURE DIASTOLIC ABNORMAL	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
BLOOD UREA INCREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
ELECTROCARDIOGRAM PR SHORTENED	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ELECTROCARDIOGRAM QT PROLONGED	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
ELECTROCARDIOGRAM ST SEGMENT ELEVATION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HAEMATOCRIT INCREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
NEUTROPHIL COUNT INCREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
PEDAL PULSE ABNORMAL	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
PLATELET COUNT DECREASED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
WAIST CIRCUMFERENCE INCREASED	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
WHITE BLOOD CELL COUNT INCREASED	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HYPOKALAEMIA	3/42 (7.1%)		3/45 (6.7%)		2/62 (3.2%)
Metabolism and nutrition disorders
DECREASED APPETITE	12/42 (28.6%)		5/45 (11.1%)		27/62 (43.5%)
HYPOALBUMINAEMIA	8/42 (19%)		6/45 (13.3%)		11/62 (17.7%)
DEHYDRATION	2/42 (4.8%)		4/45 (8.9%)		9/62 (14.5%)
HYPONATRAEMIA	3/42 (7.1%)		2/45 (4.4%)		8/62 (12.9%)
HYPOMAGNESAEMIA	4/42 (9.5%)		3/45 (6.7%)		4/62 (6.5%)
HYPERKALAEMIA	1/42 (2.4%)		5/45 (11.1%)		4/62 (6.5%)
HYPOCALCAEMIA	1/42 (2.4%)		3/45 (6.7%)		3/62 (4.8%)
CACHEXIA	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
HYPERPHOSPHATAEMIA	1/42 (2.4%)		2/45 (4.4%)		0/62 (0%)
HYPERGLYCAEMIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
HYPERURICAEMIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
MALNUTRITION	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
DYSLIPIDAEMIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
HYPERCALCAEMIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
HYPOCHOLESTEROLAEMIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HYPOGLYCAEMIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
HYPOPHOSPHATAEMIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
HYPOVOLAEMIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
MYALGIA	4/42 (9.5%)		4/45 (8.9%)		6/62 (9.7%)
PAIN IN EXTREMITY	6/42 (14.3%)		2/45 (4.4%)		4/62 (6.5%)
ARTHRALGIA	6/42 (14.3%)		1/45 (2.2%)		3/62 (4.8%)
BACK PAIN	4/42 (9.5%)		3/45 (6.7%)		1/62 (1.6%)
MUSCLE SPASMS	2/42 (4.8%)		3/45 (6.7%)		2/62 (3.2%)
MUSCULOSKELETAL PAIN	2/42 (4.8%)		4/45 (8.9%)		1/62 (1.6%)
MUSCULOSKELETAL CHEST PAIN	1/42 (2.4%)		0/45 (0%)		2/62 (3.2%)
NECK PAIN	1/42 (2.4%)		0/45 (0%)		2/62 (3.2%)
PAIN IN JAW	0/42 (0%)		0/45 (0%)		3/62 (4.8%)
BONE PAIN	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
GROIN PAIN	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
MUSCULAR WEAKNESS	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
JOINT ANKYLOSIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
MYOPATHY	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
OSTEOARTHRITIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SEBORRHOEIC KERATOSIS	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
OESOPHAGEAL CANCER METASTATIC	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
TUMOUR HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
TUMOUR INVASION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Nervous system disorders
DIZZINESS	3/42 (7.1%)		5/45 (11.1%)		7/62 (11.3%)
NEUROPATHY PERIPHERAL	2/42 (4.8%)		4/45 (8.9%)		4/62 (6.5%)
HEADACHE	1/42 (2.4%)		2/45 (4.4%)		4/62 (6.5%)
MEMORY IMPAIRMENT	1/42 (2.4%)		2/45 (4.4%)		1/62 (1.6%)
DYSGEUSIA	0/42 (0%)		3/45 (6.7%)		0/62 (0%)
SOMNOLENCE	0/42 (0%)		0/45 (0%)		3/62 (4.8%)
HYPOAESTHESIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
PARAESTHESIA	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
SYNCOPE	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
TREMOR	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
AKATHISIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
BALANCE DISORDER	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
DIZZINESS POSTURAL	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
DYSKINESIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HYPOGEUSIA	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
LETHARGY	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
NEURALGIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SPINAL CORD COMPRESSION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
VIITH NERVE PARALYSIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
VOCAL CORD PARALYSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Psychiatric disorders
INSOMNIA	4/42 (9.5%)		1/45 (2.2%)		6/62 (9.7%)
ANXIETY	1/42 (2.4%)		0/45 (0%)		3/62 (4.8%)
AGITATION	0/42 (0%)		0/45 (0%)		3/62 (4.8%)
DELIRIUM	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
DEPRESSION	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
DISORIENTATION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
EMOTIONAL DISTRESS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
FLAT AFFECT	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RESTLESSNESS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Renal and urinary disorders
RENAL FAILURE	3/42 (7.1%)		1/45 (2.2%)		4/62 (6.5%)
PROTEINURIA	1/42 (2.4%)		2/45 (4.4%)		1/62 (1.6%)
ACUTE KIDNEY INJURY	1/42 (2.4%)		2/45 (4.4%)		0/62 (0%)
DYSURIA	2/42 (4.8%)		1/45 (2.2%)		0/62 (0%)
CHROMATURIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
GLYCOSURIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HAEMATURIA	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
HYDRONEPHROSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
NEUROGENIC BLADDER	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
NOCTURIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
POLLAKIURIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RENAL ATROPHY	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
RENAL HYPERTROPHY	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RENAL IMPAIRMENT	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
URETERIC OBSTRUCTION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
URINARY HESITATION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
URINARY RETENTION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Reproductive system and breast disorders
SCROTAL OEDEMA	1/42 (2.4%)		0/45 (0%)		2/62 (3.2%)
NIPPLE PAIN	0/42 (0%)		2/45 (4.4%)		0/62 (0%)
VAGINAL DISCHARGE	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
VAGINAL HAEMORRHAGE	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
BREAST MASS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
BREAST SWELLING	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BREAST TENDERNESS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
DYSPAREUNIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
NIPPLE DISORDER	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
PENILE OEDEMA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SCROTAL SWELLING	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
TESTICULAR SWELLING	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	2/42 (4.8%)		5/45 (11.1%)		12/62 (19.4%)
PLEURAL EFFUSION	3/42 (7.1%)		1/45 (2.2%)		6/62 (9.7%)
COUGH	4/42 (9.5%)		2/45 (4.4%)		2/62 (3.2%)
DYSPNOEA EXERTIONAL	3/42 (7.1%)		1/45 (2.2%)		1/62 (1.6%)
HICCUPS	1/42 (2.4%)		2/45 (4.4%)		2/62 (3.2%)
OROPHARYNGEAL PAIN	2/42 (4.8%)		1/45 (2.2%)		2/62 (3.2%)
PULMONARY EMBOLISM	0/42 (0%)		2/45 (4.4%)		2/62 (3.2%)
NASAL CONGESTION	0/42 (0%)		2/45 (4.4%)		1/62 (1.6%)
PRODUCTIVE COUGH	1/42 (2.4%)		1/45 (2.2%)		1/62 (1.6%)
RHINORRHOEA	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
SINUS CONGESTION	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
ASPIRATION	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
ATELECTASIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
HAEMOPTYSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
HYPOXIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
PNEUMOTHORAX	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
PULMONARY OEDEMA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RESPIRATORY TRACT CONGESTION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
TACHYPNOEA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
WHEEZING	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
Skin and subcutaneous tissue disorders
RASH	3/42 (7.1%)		3/45 (6.7%)		5/62 (8.1%)
ALOPECIA	2/42 (4.8%)		0/45 (0%)		0/62 (0%)
DRY SKIN	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
ERYTHEMA	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
HYPERHIDROSIS	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
NAIL DISORDER	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
NIGHT SWEATS	2/42 (4.8%)		0/45 (0%)		0/62 (0%)
PHOTOSENSITIVITY REACTION	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
PRURITUS	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
RASH ERYTHEMATOUS	0/42 (0%)		0/45 (0%)		2/62 (3.2%)
RASH VESICULAR	0/42 (0%)		1/45 (2.2%)		1/62 (1.6%)
SKIN HYPERPIGMENTATION	1/42 (2.4%)		0/45 (0%)		1/62 (1.6%)
SWELLING FACE	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
ACTINIC KERATOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
BLISTER	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
DERMATITIS ACNEIFORM	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
HYPERKERATOSIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
INGROWING NAIL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
ONYCHOCLASIS	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
ONYCHOLYSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
RASH GENERALISED	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
RASH MACULO-PAPULAR	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
RASH PRURITIC	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
SKIN EXFOLIATION	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
SKIN LESION	0/42 (0%)		1/45 (2.2%)		0/62 (0%)
SKIN MASS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SKIN ULCER	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
STASIS DERMATITIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
URTICARIA	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
Vascular disorders
DEEP VEIN THROMBOSIS	1/42 (2.4%)		0/45 (0%)		3/62 (4.8%)
HYPOTENSION	1/42 (2.4%)		0/45 (0%)		2/62 (3.2%)
HYPERTENSION	1/42 (2.4%)		1/45 (2.2%)		0/62 (0%)
HOT FLUSH	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
SUBCLAVIAN VEIN THROMBOSIS	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
THROMBOPHLEBITIS SUPERFICIAL	1/42 (2.4%)		0/45 (0%)		0/62 (0%)
THROMBOSIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)
VENOUS THROMBOSIS	0/42 (0%)		0/45 (0%)		1/62 (1.6%)

Limitations/Caveats

It was not possible to calculate data for PK parameters such as t1/2, AUC0-inf, CL/f, Vz/f, λz because dosing interval was too small compared to the long half-life to characterize terminal phase rate constant, which is needed for the calculation.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.