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Trial record 24 of 42 for:    Malignant Hyperthermia 5

Trial of MSC1936369B in Subjects With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00982865
Recruitment Status : Completed
First Posted : September 23, 2009
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Merck Serono S.A., Geneva
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Solid Tumors
Cancer
Intervention Drug: MSC1936369B
Enrollment 182
Recruitment Details First/last subject (informed consent): December 2007/March 2012. Last subject completed: April 2016.
Pre-assignment Details A total of 182 subjects entered the trial, of which 2 did not receive any treatment. 180 subjects received the study treatment and were included in the subject disposition table.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily (BID)
Hide Arm/Group Description Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2. Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Period Title: Overall Study
Started 49 82 15 34
Completed 49 82 15 34
Not Completed 0 0 0 0
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily Total
Hide Arm/Group Description Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2. Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Total of all reporting groups
Overall Number of Baseline Participants 49 82 15 34 180
Hide Baseline Analysis Population Description
Safety analysis set included all subjects who received at least 1 dose of MSC1936369B treatment.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 49 participants 82 participants 15 participants 34 participants 180 participants
>= 18 − <45 Years 4 10 4 7 25
>=45 − <65 Years 30 49 9 13 101
>=65 Years 15 23 2 14 54
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 82 participants 15 participants 34 participants 180 participants
Female
20
  40.8%
30
  36.6%
9
  60.0%
11
  32.4%
70
  38.9%
Male
29
  59.2%
52
  63.4%
6
  40.0%
23
  67.6%
110
  61.1%
1.Primary Outcome
Title Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21
Hide Description DLT was defined as any of following toxicities at any dose level according to using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) v3.0(CTCAE), probably or possibly related to trial medication by investigator or sponsor: a)Any Grade 3 or more non-haematological toxicity excluding: (i)Grade 3 asymptomatic increase in liver function tests (Aspartate Aminotransferase, Alanine transaminase, Alkaline Phosphatase reversible within 7 days for subjects without liver involvement, or grade 4 for subjects with liver involvement; (ii)Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. serotonin [5HT3] antagonists and corticosteroids); (iii)Grade 3 diarrhoea if it is encountered despite adequate and optimal anti diarrhoea therapy; b)Grade 4 neutropenia of >5 days duration or febrile neutropenia lasting for more than 1 day; c)Grade 4 thrombocytopenia >1 day or grade 3 with bleeding; d)Any treatment delay >2 weeks due to drug-related AEs.
Time Frame Day 1 up to Day 21 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description

Dose Escalation Analysis Set included all subjects who meet at least 1 of following criteria:

subjects who experienced any DLT during Cycle 1 & who received planned treatment.

Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Hide Arm/Group Description:
Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.
Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 44 74 15 33
Measure Type: Number
Unit of Measure: Subjects
2 6 0 6
2.Secondary Outcome
Title Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation
Hide Description AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 253 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs.
Time Frame Baseline up to 253 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF) included all subjects who received at least 1 dose of MSC1936369B treatment.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Hide Arm/Group Description:
Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.
Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 49 82 15 34
Measure Type: Number
Unit of Measure: Subjects
TEAEs 47 82 15 34
Serious TEAEs 23 45 8 21
TEAEs leading to discontinuation 13 22 2 6
3.Secondary Outcome
Title Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death
Hide Description [Not Specified]
Time Frame Baseline up to 253 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ALL subject analysis set was used which included all the subjects who signed the informed consent form and entered the study.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Hide Arm/Group Description:
Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.
Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 49 83 15 35
Measure Type: Number
Unit of Measure: Subjects
10 14 2 2
4.Secondary Outcome
Title Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events
Hide Description Any clinically significant changes in laboratory evaluations and vital signs were recorded as treatment emergent adverse events. The clinical laboratory parameters that were assessed included: Hematological parameters, Blood chemistry parameters, Urinalysis and the vital signs that were assessed included: Blood pressure, Heart rate, Temperature and Weight. SAF analysis was used.
Time Frame Baseline up to 253 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
SAF analysis was used.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Hide Arm/Group Description:
Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.
Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 49 82 15 34
Measure Type: Number
Unit of Measure: Subjects
Haemoglobin decreased 1 2 0 0
Anaemia 10 23 3 3
Lymphopenia 3 7 0 0
Thrombocytopenia 3 6 2 1
Platelet count decreased 0 1 0 0
Neutropenia 0 4 0 1
Leukopenia 0 0 1 0
Pancytopenia 0 0 0 1
Hyponatraemia 0 1 0 1
Hypokalaemia 4 10 2 2
Hyperkalaemia 1 0 0 0
Hypocalcaemia 2 7 0 1
Hypercalcaemia 0 3 0 0
Hypomagnesaemia 2 3 2 0
Hypophosphataemia 0 2 0 0
Hepatic enzyme increased 0 1 0 0
Hepatic function abnormal 0 1 0 0
Alanine aminotransferase increased 0 1 0 2
Aspartate aminotransferase increased 1 1 0 2
Blood alkaline phosphatase increased 1 0 0 1
Hyperbilirubinaemia 1 1 0 0
Blood lactate dehydrogenase increased 1 0 0 1
Blood creatine phosphokinase increased 1 2 1 5
Blood creatinine increased 0 1 0 0
Blood 25−hydroxycholecalciferol decreased 1 1 0 0
Vitamin D decreased 0 1 0 0
Blood parathyroid hormone increased 1 1 0 0
Hyperglycaemia 0 1 0 0
C−reactive protein increased 0 1 0 0
Proteinuria 0 0 1 1
Hyperthyroidism 0 0 0 1
Hypoalbuminaemia 3 4 0 2
Weight increased 0 3 0 3
Weight decreased 6 8 4 2
Hyperthermia 1 5 0 1
Hypertension 7 5 1 4
Hypotension 3 1 2 0
Heart rate increased 1 0 0 0
Tachycardia 3 0 2 0
Blood potassium increased 1 0 0 0
5.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1
Hide Description Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours (h) post-dose on Cycle 1(C1) Day 1 (D1), Cycle 1 Day 12 (D12) and Cycle 3 (C3) Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: subjects received at least 1 dose of drug & provided sufficient PK serum samples for at least 1st 24h following 1st dose of C1D1. Number of Participants Analyzed=subjects evaluable for this endpoint & Number analyzed=subjects evaluated at specified time point & “0”indicates no subject analyzed for that specific time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 4 3 3 3 3 3 6 3 4 3 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
C1D1 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 13 participants
2.02
(41.0%)
3.20
(45.5%)
4.21
(47.9%)
6.69
(62.9%)
12.60
(15.4%)
62.32
(33.6%)
126.21
(70.2%)
212.96
(106.3%)
357.39
(30.7%)
325.99
(31.8%)
428.85
(57.9%)
C1D12 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 11 participants
2.92
(39.0%)
2.69
(10.1%)
6.29
(40.6%)
9.75
(63.3%)
21.93
(110.5%)
54.47
(116.2%)
150.67
(78.1%)
175.94
(47.5%)
413.58
(9.1%)
602.12
(11.0%)
425.26
(71.0%)
C3D1 Number Analyzed 1 participants 1 participants 1 participants 3 participants 3 participants 1 participants 3 participants 2 participants 0 participants 2 participants 7 participants
2.00 [1] 
(NA%)
2.90 [1] 
(NA%)
5.60 [1] 
(NA%)
8.06
(30.3%)
10.90
(68.5%)
51.30 [1] 
(NA%)
84.70
(78.8%)
167.75
(15.5%)
282.44
(14.9%)
652.70
(48.3%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
6.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description Cmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed= 0 as no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 3 3 3 3 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
1.65
(59.2%)
2.87
(56.6%)
4.55
(113.4%)
17.26
(27.8%)
30.90
(32.6%)
39.19
(69.7%)
187.98
(39.7%)
321.85
(32.7%)
306.63
(110.4%)
373.59
(24.9%)
605.11
(48.8%)
539.02
(78.0%)
680.87
(45.6%)
990.92
(64.9%)
C1D15 Number Analyzed 3 participants 3 participants 3 participants 3 participants 2 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 10 participants 11 participants 4 participants
2.28
(58.0%)
7.77
(96.2%)
4.21
(39.9%)
18.78
(32.2%)
18.47
(33.1%)
34.87
(36.8%)
131.71
(14.7%)
286.88
(21.8%)
539.17
(37.1%)
432.46
(7.6%)
492.81
(117.1%)
450.29
(67.4%)
629.85
(71.3%)
1535.60
(57.1%)
C3D1 Number Analyzed 2 participants 1 participants 2 participants 2 participants 1 participants 0 participants 1 participants 0 participants 2 participants 1 participants 2 participants 8 participants 7 participants 3 participants
1.25
(5.7%)
4.30 [1] 
(NA%)
6.56
(39.8%)
14.81
(50.1%)
16.10 [1] 
(NA%)
96.60 [1] 
(NA%)
710.94
(57.4%)
532.80 [1] 
(NA%)
568.49
(76.2%)
795.86
(50.0%)
773.14
(51.0%)
2344.91
(23.1%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
7.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description Cmax was obtained directly from the concentration versus time curve. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set included all subjects who fulfilled following conditions: Food & drink intake, trial medication administration according to protocol, & not excreted irregularly, PK samples collected. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this endpoint.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Fasted
321.14
(58.3%)
1158.00 [1] 
(NA%)
Fed
305.94
(45.6%)
370.70 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
8.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily
Hide Description Cmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies the subjects who were evaluated at that specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D1 Number Analyzed 3 participants 12 participants
241.27
(47.0%)
402.77
(59.2%)
C1D15 Number Analyzed 3 participants 12 participants
316.08
(34.9%)
324.80
(65.8%)
C3D1 Number Analyzed 2 participants 10 participants
473.27
(38.7%)
376.62
(45.2%)
9.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily
Hide Description Cmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 18 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D1 Number Analyzed 3 participants 18 participants 13 participants
132.57
(40.2%)
206.46
(41.7%)
263.08
(68.5%)
C1D15 Number Analyzed 3 participants 18 participants 11 participants
178.09
(95.0%)
231.12
(44.0%)
190.42
(57.6%)
C3D1 Number Analyzed 2 participants 13 participants 6 participants
139.60
(26.6%)
157.46
(53.7%)
329.28
(73.5%)
10.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1
Hide Description Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed= 0 as no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 4 3 3 3 3 3 6 3 4 3 13
Median (Full Range)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 13 participants
1.500
(1.02 to 1.53)
0.750
(0.50 to 4.25)
1.500
(1.00 to 2.50)
1.500
(1.00 to 2.17)
1.500
(1.00 to 2.50)
1.000
(0.50 to 2.00)
1.500
(1.00 to 4.00)
1.017
(1.00 to 2.50)
1.000
(0.98 to 1.50)
1.483
(0.52 to 2.17)
1.017
(0.50 to 6.00)
C1D12 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 11 participants
1.633
(0.50 to 2.50)
0.533
(0.33 to 2.00)
1.000
(1.00 to 2.50)
1.000
(1.00 to 1.08)
1.017
(1.00 to 1.05)
1.500
(1.50 to 1.50)
1.000
(0.50 to 3.92)
2.000
(0.75 to 2.52)
1.000
(0.50 to 4.00)
1.500
(1.50 to 2.00)
1.083
(0.52 to 8.00)
C3D1 Number Analyzed 1 participants 1 participants 1 participants 3 participants 3 participants 1 participants 3 participants 2 participants 0 participants 2 participants 7 participants
1.52
(1.52 to 1.52)
0.500
(0.50 to 0.50)
1.52
(1.52 to 1.52)
1.000
(0.50 to 2.67)
1.517
(1.00 to 4.05)
1.500
(1.50 to 1.50)
1.000
(1.00 to 3.58)
1.508
(0.50 to 2.52)
1.767
(1.50 to 2.03)
2.000
(0.50 to 4.00)
11.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed= 0 as no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 3 3 3 3 5 3 3 3 3 4 14 12 5
Median (Full Range)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
1.500
(1.50 to 1.92)
1.017
(0.50 to 2.50)
1.500
(1.00 to 2.00)
1.000
(0.50 to 24.98)
0.533
(0.52 to 2.00)
1.500
(0.50 to 4.00)
1.000
(0.58 to 2.02)
0.500
(0.50 to 1.02)
1.000
(0.47 to 1.50)
1.500
(0.50 to 1.58)
1.250
(0.33 to 2.02)
1.500
(0.58 to 4.00)
1.250
(0.50 to 2.50)
2.000
(0.50 to 2.50)
C1D15 Number Analyzed 3 participants 3 participants 3 participants 3 participants 2 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 10 participants 11 participants 4 participants
1.500
(1.42 to 2.00)
0.967
(0.52 to 1.50)
2.000
(0.43 to 2.00)
0.667
(0.50 to 2.50)
1.008
(1.00 to 1.02)
1.500
(1.50 to 4.00)
1.017
(0.50 to 2.12)
1.500
(0.67 to 1.52)
1.250
(1.00 to 1.50)
1.500
(1.50 to 2.02)
2.000
(1.00 to 2.08)
1.517
(1.00 to 7.92)
1.250
(0.50 to 3.00)
1.458
(1.00 to 2.00)
C3D1 Number Analyzed 2 participants 1 participants 2 participants 2 participants 1 participants 0 participants 1 participants 0 participants 2 participants 1 participants 2 participants 8 participants 7 participants 3 participants
1.250
(1.00 to 1.50)
2.000
(2.00 to 2.00)
1.258
(1.00 to 1.52)
1.000
(1.00 to 1.00)
2.500
(2.50 to 2.50)
1.50
(1.50 to 1.50)
0.500
(0.50 to 0.50)
2.000
(2.00 to 2.00)
1.042
(0.58 to 1.50)
1.333
(1.00 to 2.10)
1.000
(0.50 to 2.02)
1.000
(1.00 to 1.67)
12.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Median (Full Range)
Unit of Measure: Hours (h)
Fasted
1.600
(0.33 to 2.50)
1.000
(1.00 to 1.00)
Fed
2.033
(1.50 to 4.00)
6.000
(6.00 to 6.00)
13.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily
Hide Description Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Median (Full Range)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 3 participants 12 participants
1.033
(1.00 to 1.50)
1.500
(0.50 to 2.03)
C1D15 Number Analyzed 3 participants 12 participants
2.500
(1.52 to 2.50)
1.492
(0.50 to 4.00)
C3D1 Number Analyzed 2 participants 10 participants
2.000
(1.50 to 2.50)
1.000
(0.57 to 2.10)
14.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily
Hide Description Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 18 13
Median (Full Range)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 3 participants 18 participants 13 participants
1.500
(1.00 to 2.00)
1.000
(0.50 to 4.00)
0.667
(0.47 to 2.50)
C1D15 Number Analyzed 3 participants 18 participants 11 participants
1.500
(1.03 to 2.00)
1.500
(0.50 to 2.55)
1.500
(0.97 to 4.08)
C3D1 Number Analyzed 2 participants 13 participants 6 participants
1.467
(0.92 to 2.02)
1.183
(0.50 to 2.07)
1.467
(0.50 to 1.57)
15.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 1
Hide Description Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed= 0 as no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 4 3 3 3 3 3 6 3 4 3 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanogram per milliliter (h*ng/mL)
C1D1 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 13 participants
4.6
(431.3%)
5.2
(63.9%)
18.5
(49.8%)
22.7
(29.2%)
52.7
(74.5%)
213.9
(84.0%)
531.3
(55.4%)
889.0
(31.9%)
1624.8
(36.1%)
1748.1
(38.8%)
2292.4
(52.5%)
C1D12 Number Analyzed 4 participants 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 11 participants
7.0
(269.8%)
6.0
(89.3%)
26.0
(55.0%)
35.9
(79.7%)
83.6
(67.7%)
182.0
(125.1%)
691.9
(51.4%)
880.0
(45.7%)
1900.3
(99.7%)
1991.4
(19.2%)
1682.4
(52.4%)
C3D1 Number Analyzed 1 participants 1 participants 1 participants 3 participants 3 participants 1 participants 3 participants 2 participants 0 participants 2 participants 7 participants
6.9 [1] 
(NA%)
2.7 [1] 
(NA%)
21.0 [1] 
(NA%)
23.0
(38.2%)
45.2
(51.8%)
113.2 [1] 
(NA%)
334.9
(47.8%)
666.3
(52.3%)
876.7
(20.4%)
2064.1
(55.0%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
16.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: : Regimen 2 (Without Food Effect)
Hide Description Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number Analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 3 3 3 3 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
1.9
(331.6%)
8.2
(53.1%)
6.7
(292.9%)
67.9
(93.9%)
74.4
(19.4%)
188.4
(61.7%)
625.7
(20.6%)
808.0
(15.7%)
861.1
(112.4%)
1484.6
(13.0%)
2287.0
(96.6%)
2216.5
(75.7%)
3415.6
(44.5%)
4041.3
(60.8%)
C1D15 Number Analyzed 3 participants 3 participants 3 participants 3 participants 2 participants 3 participants 3 participants 3 participants 3 participants 3 participants 3 participants 10 participants 11 participants 4 participants
4.3
(228.5%)
22.2
(42.1%)
13.8
(66.9%)
79.3
(57.9%)
67.8
(53.9%)
161.5
(14.1%)
621.2
(12.7%)
906.3
(15.4%)
1553.9
(122.5%)
1826.2
(17.9%)
1862.3
(96.4%)
2086.6
(69.9%)
3436.8
(64.7%)
5765.9
(15.3%)
C3D1 Number Analyzed 2 participants 1 participants 2 participants 2 participants 1 participants 0 participants 1 participants 0 participants 2 participants 1 participants 2 participants 8 participants 7 participants 3 participants
0.5
(76.6%)
10.2 [1] 
(NA%)
26.2
(15.6%)
40.5
(26.9%)
46.1 [1] 
(NA%)
306.2 [1] 
(NA%)
1394.7
(24.6%)
1299.3 [1] 
(NA%)
2053.6
(71.1%)
2171.2
(59.4%)
2484.5
(53.6%)
4906.3
(19.2%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
17.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
Fasted
1509.6
(46.6%)
3286 [1] 
(NA%)
Fed
1458.3
(41.3%)
5072.9 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
18.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 3 Once Daily
Hide Description Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 3 participants 12 participants
1229.3
(96.5%)
1544.9
(57.1%)
C1D15 Number Analyzed 3 participants 12 participants
1532.4
(80.4%)
1428.8
(63.6%)
C3D1 Number Analyzed 2 participants 10 participants
1392.3
(35.2%)
1122.5
(45.2%)
19.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of MSC1936369B: Regimen 3 Twice Daily
Hide Description Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 18 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 3 participants 18 participants 13 participants
407.2
(40.7%)
681.4
(43.7%)
791.1
(62.3%)
C1D15 Number Analyzed 3 participants 18 participants 11 participants
589.3
(66.5%)
838.8
(43.9%)
710.3
(65.0%)
C3D1 Number Analyzed 2 participants 13 participants 6 participants
450.0
(57.1%)
577.0
(72.5%)
1005.0
(25.6%)
20.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra 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 Lower Limit of quantification (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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 2 1 3 3 3 3 6 3 4 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 2 participants 1 participants 3 participants 3 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 12 participants
136.2
(9.2%)
6.2 [1] 
(NA%)
55.5
(321.8%)
31.4
(29.7%)
61.3
(66.9%)
234.1
(70.2%)
574.2
(50.0%)
924.2
(32.7%)
1699.7
(36.1%)
1836.4
(42.8%)
2773.5
(54.7%)
C1D12 Number Analyzed 2 participants 1 participants 3 participants 3 participants 3 participants 3 participants 4 participants 3 participants 3 participants 3 participants 9 participants
38.3
(254.8%)
9.4 [1] 
(NA%)
43.8
(58.7%)
47.5
(68.1%)
105.6
(57.6%)
206.3
(106.5%)
805.6
(58.9%)
960.7
(46.9%)
2108.2
(115.0%)
2257.6
(30.1%)
2022.8
(41.3%)
C3D1 Number Analyzed 1 participants 0 participants 1 participants 3 participants 2 participants 1 participants 2 participants 2 participants 0 participants 2 participants 6 participants
15.4 [1] 
(NA%)
47.6 [1] 
(NA%)
34.4
(37.6%)
55.5
(90.0%)
134.5 [1] 
(NA%)
489.8
(55.2%)
1072.1
(121.6%)
1056.0
(26.6%)
3477.6
(102.0%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
21.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra 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 was at or above the Lower Limit of quantification (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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 2 3 3 3 3 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 0 participants 2 participants 2 participants 2 participants 3 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
23.4
(65.7%)
23.6
(22.5%)
59.1
(6.2%)
90.3
(30.8%)
218.4
(62.1%)
646.9
(20.7%)
820.4
(15.7%)
885.8
(111.0%)
1525.6
(13.2%)
2424.2
(109.7%)
2287.8
(77.4%)
3602.2
(46.2%)
4300.3
(54.2%)
C1D15 Number Analyzed 2 participants 3 participants 3 participants 3 participants 2 participants 2 participants 3 participants 3 participants 3 participants 3 participants 3 participants 8 participants 10 participants 4 participants
15.7
(10.6%)
33.3
(45.8%)
21.9
(91.5%)
102.0
(63.6%)
89.7
(85.9%)
172.2
(9.0%)
669.1
(10.5%)
933.9
(15.4%)
1665.2
(132.1%)
1893.2
(17.5%)
2129.0
(123.7%)
2029.9
(63.3%)
3900.8
(64.3%)
6232.1
(7.0%)
C3D1 Number Analyzed 0 participants 1 participants 2 participants 2 participants 1 participants 0 participants 1 participants 0 participants 2 participants 1 participants 2 participants 8 participants 7 participants 3 participants
15.4 [1] 
(NA%)
41.2
(41.4%)
49.5
(17.4%)
58.1 [1] 
(NA%)
415.6 [1] 
(NA%)
1655.1
(19.1%)
1584.8 [1] 
(NA%)
2461.3
(64.3%)
2796.2
(59.3%)
3452.9
(61.6%)
5651.1
(23.5%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
22.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra 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 Lower Limit of quantification (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. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
Fasted
1580.6
(48.7%)
3344.3 [1] 
(NA%)
Fed
1495.7
(41.8%)
5633.8 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
23.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra 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 Lower Limit of quantification (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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 18 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 3 participants 17 participants 13 participants
527.6
(57.4%)
742.3
(47.1%)
939.9
(67.3%)
C1D15 Number Analyzed 3 participants 18 participants 11 participants
674.1
(73.6%)
1004.2
(46.4%)
978.4
(63.7%)
C3D1 Number Analyzed 2 participants 13 participants 6 participants
696.0
(101.4%)
700.8
(79.0%)
1285.7
(29.0%)
24.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra 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 Lower Limit of quantification (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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*ng/mL
C1D1 Number Analyzed 3 participants 12 participants
1253.1
(96.9%)
1581.4
(56.6%)
C1D15 Number Analyzed 3 participants 12 participants
1753.9
(93.1%)
1517.1
(65.6%)
C3D1 Number Analyzed 2 participants 10 participants
1597.0
(50.7%)
1400.3
(53.0%)
25.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1
Hide Description 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. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 2 3 3 6 3 4 3 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 10 participants
3.346 [1] 
(NA%)
3.405
(52.1%)
4.599
(29.1%)
4.781
(39.4%)
5.389
(9.4%)
5.335
(23.6%)
5.351
(15.9%)
5.247
(17.1%)
C1D12 Number Analyzed 0 participants 0 participants 0 participants 2 participants 1 participants 3 participants 4 participants 3 participants 3 participants 2 participants 8 participants
4.985
(123.5%)
9.249 [1] 
(NA%)
3.236
(19.4%)
6.750
(21.5%)
4.688
(60.4%)
6.926
(33.6%)
5.672
(15.4%)
3.964
(44.7%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 3 participants
2.959 [1] 
(NA%)
2.811 [1] 
(NA%)
2.931 [1] 
(NA%)
2.842 [1] 
(NA%)
3.038
(3.4%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
26.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description 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. As AUCextra was >20% of AUC0-inf, t1/2 derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 1 2 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours (h)
C1D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 2 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
2.594
(5.0%)
5.119
(30.5%)
5.115
(6.6%)
4.187
(10.3%)
3.305
(84.0%)
4.826
(14.0%)
5.057
(45.3%)
4.904
(18.8%)
5.641
(21.6%)
4.313
(29.6%)
C1D15 Number Analyzed 0 participants 0 participants 0 participants 1 participants 1 participants 2 participants 3 participants 3 participants 3 participants 3 participants 2 participants 7 participants 10 participants 4 participants
2.941 [1] 
(NA%)
2.335 [1] 
(NA%)
4.443
(67.3%)
6.646
(19.5%)
5.277
(8.0%)
6.441
(28.4%)
5.193
(11.1%)
4.851
(7.9%)
5.479
(14.1%)
6.016
(18.9%)
4.847
(16.4%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants 2 participants 1 participants 2 participants 4 participants 3 participants 2 participants
2.732 [1] 
(NA%)
3.477
(11.0%)
2.853 [1] 
(NA%)
2.863
(22.0%)
2.418
(25.2%)
2.628
(9.4%)
2.260
(34.4%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
27.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description 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. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour (h)
Fasted
4.898
(36.7%)
4.452 [1] 
(NA%)
Fed
4.534
(18.3%)
6.123 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
28.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily
Hide Description 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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour (h)
C1D1 Number Analyzed 3 participants 12 participants
4.236
(1.3%)
4.097
(33.5%)
C1D15 Number Analyzed 2 participants 12 participants
5.259
(14.8%)
5.599
(30.1%)
C3D1 Number Analyzed 1 participants 6 participants
1.780 [1] 
(NA%)
2.680
(21.1%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
29.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily
Hide Description 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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 17 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour (h)
C1D1 Number Analyzed 1 participants 17 participants 12 participants
2.050 [1] 
(NA%)
2.509
(25.1%)
2.814
(20.2%)
C1D15 Number Analyzed 3 participants 14 participants 7 participants
2.890
(23.8%)
3.265
(18.6%)
3.210
(23.8%)
C3D1 Number Analyzed 1 participants 7 participants 2 participants
3.144 [1] 
(NA%)
2.636
(17.0%)
3.260
(10.6%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
30.Secondary Outcome
Title Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1
Hide Description Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 2 3 3 6 3 4 3 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
C1D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 10 participants
132.69 [1] 
(NA%)
114.26
(66.9%)
59.80
(70.2%)
48.76
(50.0%)
48.69
(32.7%)
40.01
(36.1%)
50.45
(41.2%)
47.82
(53.3%)
C1D12 Number Analyzed 0 participants 0 participants 0 participants 2 participants 1 participants 3 participants 4 participants 3 participants 3 participants 2 participants 8 participants
70.60
(77.3%)
44.55 [1] 
(NA%)
62.53
(92.6%)
37.49
(55.2%)
49.37
(43.8%)
35.80
(99.7%)
50.88
(19.6%)
61.44
(42.3%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 3 participants
217.56 [1] 
(NA%)
104.07 [1] 
(NA%)
82.35 [1] 
(NA%)
107.06 [1] 
(NA%)
72.25
(35.7%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
31.Secondary Outcome
Title Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf. As AUCextra was >20% of AUC0-inf, CL/f derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 1 2 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
C1D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 2 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
90.76
(18.3%)
64.09
(62.1%)
43.28
(20.7%)
54.85
(15.7%)
76.77
(111.0%)
61.61
(13.2%)
49.50
(109.7%)
65.57
(77.4%)
54.13
(46.2%)
60.63
(53.4%)
C1D15 Number Analyzed 0 participants 0 participants 0 participants 1 participants 1 participants 2 participants 3 participants 3 participants 3 participants 3 participants 2 participants 7 participants 10 participants 4 participants
59.55 [1] 
(NA%)
134.9 [1] 
(NA%)
86.72
(12.5%)
45.10
(12.7%)
49.65
(15.4%)
43.76
(122.4%)
51.47
(17.9%)
92.42
(84.1%)
81.22
(65.4%)
53.49
(64.3%)
42.20
(5.9%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants 2 participants 1 participants 2 participants 4 participants 3 participants 2 participants
89.34 [1] 
(NA%)
41.08
(19.1%)
59.31 [1] 
(NA%)
48.76
(64.3%)
61.04
(53.0%)
72.33
(63.8%)
44.23
(37.5%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
32.Secondary Outcome
Title Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
Fasted
56.94
(48.7%)
44.85 [1] 
(NA%)
Fed
60.17
(41.8%)
26.62 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
33.Secondary Outcome
Title Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily
Hide Description Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
C1D1 Number Analyzed 3 participants 12 participants
47.88
(96.9%)
56.91
(56.6%)
C1D15 Number Analyzed 2 participants 12 participants
48.31
(103.9%)
62.85
(63.6%)
C3D1 Number Analyzed 1 participants 6 participants
53.36 [1] 
(NA%)
75.63
(59.6%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
34.Secondary Outcome
Title Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily
Hide Description Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 17 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour
C1D1 Number Analyzed 1 participants 17 participants 12 participants
114.82 [1] 
(NA%)
80.83
(47.1%)
83.86
(67.2%)
C1D15 Number Analyzed 3 participants 14 participants 7 participants
71.44
(69.3%)
66.89
(52.1%)
94.48
(71.2%)
C3D1 Number Analyzed 1 participants 7 participants 2 participants
126.1 [1] 
(NA%)
103.3
(66.9%)
77.09
(21.0%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
35.Secondary Outcome
Title Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 1.5mg, 2.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 2 3 3 6 3 4 3 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
C1D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 10 participants
640.60 [1] 
(NA%)
561.27
(12.9%)
396.76
(86.7%)
336.32
(78.8%)
378.56
(23.0%)
307.90
(43.1%)
389.49
(28.6%)
361.99
(43.0%)
C1D12 Number Analyzed 0 participants 0 participants 0 participants 2 participants 1 participants 3 participants 4 participants 3 participants 3 participants 2 participants 8 participants
507.8
(28.3%)
594.5 [1] 
(NA%)
291.9
(73.0%)
365.1
(35.0%)
333.9
(65.1%)
357.8
(53.7%)
416.3
(35.8%)
351.4
(37.5%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 1 participants 1 participants 0 participants 1 participants 0 participants 1 participants 3 participants
928.91 [1] 
(NA%)
422.04 [1] 
(NA%)
348.19 [1] 
(NA%)
438.91 [1] 
(NA%)
316.63
(33.9%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
36.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect)
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. As AUCextra was >20% of AUC0-inf, Vz/F derived from λz was regarded as implausible & not calculated for arms MSC1936369B 1mg, 2mg, 3.5 mg.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 0 0 0 1 2 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
C1D1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 2 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
339.58
(13.2%)
473.32
(81.2%)
319.40
(27.0%)
331.36
(13.3%)
366.00
(22.8%)
428.99
(22.7%)
361.12
(58.1%)
463.92
(68.7%)
440.55
(41.7%)
377.28
(42.4%)
C1D15 Number Analyzed 0 participants 0 participants 0 participants 1 participants 1 participants 2 participants 3 participants 3 participants 3 participants 3 participants 2 participants 7 participants 10 participants 4 participants
252.7 [1] 
(NA%)
454.6 [1] 
(NA%)
555.9
(84.7%)
432.5
(30.7%)
378.0
(23.6%)
406.6
(76.5%)
385.6
(25.9%)
646.9
(96.3%)
642.1
(63.5%)
464.2
(64.9%)
295.1
(13.4%)
C3D1 Number Analyzed 0 participants 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants 2 participants 1 participants 2 participants 4 participants 3 participants 2 participants
352.10 [1] 
(NA%)
206.07
(30.5%)
244.16 [1] 
(NA%)
201.39
(95.6%)
212.92
(34.4%)
274.24
(53.8%)
144.24
(79.1%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
37.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect)
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here, “Number of subjects analyzed” signifies those subjects who were evaluable for this outcome Measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
Fasted
402.4
(49.0%)
288.1 [1] 
(NA%)
Fed
393.6
(40.5%)
235.2 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
38.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma 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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
C1D1 Number Analyzed 3 participants 12 participants
292.61
(99.0%)
336.38
(47.1%)
C1D15 Number Analyzed 2 participants 12 participants
366.5
(131.6%)
507.7
(66.0%)
C3D1 Number Analyzed 1 participants 6 participants
137.0 [1] 
(NA%)
292.5
(47.3%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
39.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily
Hide Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma 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, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 17 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter
C1D1 Number Analyzed 1 participants 17 participants 12 participants
339.51 [1] 
(NA%)
292.59
(42.3%)
340.43
(57.7%)
C1D15 Number Analyzed 3 participants 14 participants 7 participants
297.9
(57.8%)
315.0
(59.4%)
437.6
(59.1%)
C3D1 Number Analyzed 1 participants 7 participants 2 participants
571.8 [1] 
(NA%)
392.9
(81.9%)
362.6
(10.2%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
40.Secondary Outcome
Title Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1
Hide Description AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 12 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 1.5 mg MSC1936369B 2.5 mg MSC1936369B 3.5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 1.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 2 1 3 3 3 3 6 3 4 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage of AUC 0-∞
C1D1 Number Analyzed 2 participants 1 participants 3 participants 3 participants 3 participants 3 participants 6 participants 3 participants 4 participants 3 participants 12 participants
81.33
(21.2%)
42.23 [1] 
(NA%)
43.45
(79.8%)
26.80
(27.3%)
13.08
(47.7%)
5.31
(174.3%)
5.39
(112.5%)
3.52
(52.0%)
4.08
(47.3%)
4.09
(75.2%)
5.28
(155.8%)
C1D12 Number Analyzed 2 participants 1 participants 3 participants 3 participants 3 participants 3 participants 4 participants 3 participants 3 participants 3 participants 9 participants
50.60
(8.6%)
33.84 [1] 
(NA%)
40.60
(5.6%)
21.27
(56.8%)
19.82
(37.6%)
7.83
(193.6%)
6.57
(45.0%)
8.17
(29.1%)
6.56
(185.5%)
7.94
(131.8%)
2.97
(137.2%)
C3D1 Number Analyzed 1 participants 0 participants 1 participants 3 participants 2 participants 1 participants 2 participants 2 participants 0 participants 2 participants 6 participants
55.15 [1] 
(NA%)
55.79 [1] 
(NA%)
32.85
(14.3%)
21.27
(33.1%)
15.84 [1] 
(NA%)
28.06
(30.6%)
27.67
(126.0%)
16.54
(30.2%)
26.05
(98.7%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
41.Secondary Outcome
Title Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (Without Food Effect)
Hide Description AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number of Participants Analyzed” signifies those subjects who were evaluable for this outcome measure and “Number Analyzed” signifies those who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B 1 mg MSC1936369B 2 mg MSC1936369B 3.5 mg MSC1936369B 5 mg MSC1936369B 7 mg MSC1936369B 14 mg MSC1936369B 28 mg MSC1936369B 45 mg MSC1936369B 68 mg MSC1936369B 94 mg MSC1936369B 120 mg MSC1936369B 150 mg MSC1936369B 195 mg MSC1936369B 255 mg
Hide Arm/Group Description:
Subjects received 1 mg of MSC1936369B (capsule formulation) orally, once daily on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 2 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 3.5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 5 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 7 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 14 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 28 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 68 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 94 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 120 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 195 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 255 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 2 3 3 3 3 5 3 3 3 3 4 14 12 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage of AUC 0-∞
C1D1 Number Analyzed 0 participants 2 participants 2 participants 2 participants 3 participants 5 participants 3 participants 3 participants 3 participants 3 participants 4 participants 14 participants 12 participants 5 participants
55.78
(11.0%)
31.63
(31.2%)
27.25
(15.2%)
15.10
(63.9%)
12.17
(59.8%)
3.29
(3.7%)
1.46
(30.8%)
2.66
(40.8%)
2.60
(33.4%)
2.94
(181.0%)
2.64
(68.3%)
4.36
(76.2%)
3.57
(149.3%)
C1D15 Number Analyzed 2 participants 3 participants 3 participants 3 participants 2 participants 2 participants 3 participants 3 participants 3 participants 3 participants 3 participants 8 participants 10 participants 4 participants
40.86
(2.9%)
33.34
(6.4%)
35.29
(30.0%)
21.93
(20.2%)
19.45
(107.4%)
12.45
(58.0%)
6.89
(32.9%)
2.96
(1.9%)
5.00
(141.4%)
3.40
(33.9%)
5.82
(251.8%)
4.82
(82.9%)
5.77
(72.8%)
5.22
(112.2%)
C3D1 Number Analyzed 0 participants 1 participants 2 participants 2 participants 1 participants 0 participants 1 participants 0 participants 2 participants 1 participants 2 participants 8 participants 7 participants 3 participants
33.93 [1] 
(NA%)
33.77
(47.7%)
17.27
(45.0%)
20.68 [1] 
(NA%)
26.32 [1] 
(NA%)
15.35
(29.7%)
18.02 [1] 
(NA%)
16.22
(26.9%)
17.54
(83.4%)
23.45
(59.4%)
11.15
(77.4%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
42.Secondary Outcome
Title Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 2 (With Food Effect)
Hide Description AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf. Summarized data over Day 1 and Day 2 was reported.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24 hours post-dose on Cycle 1 Day 1 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
The food effect analysis set (FES). Here, “Number of subjects analyzed” signifies those subjects who were evaluable for this outcome Measure.
Arm/Group Title MSC1936369B 90 mg MSC1936369B 150 mg
Hide Arm/Group Description:
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Subjects received 150 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 8 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage of AUC 0-∞
Fasted
2.54
(149.8%)
1.74 [1] 
(NA%)
Fed
2.21
(56.3%)
9.96 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated as there was only 1 subject analyzed in this reporting group.
43.Secondary Outcome
Title Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily
Hide Description AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 and 24 hours post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 60 mg MSC1936369B 90 mg
Hide Arm/Group Description:
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 90 mg of MSC1936369B (capsule formulation) orally, QD on Days 1 and Day 2 of 21-day treatment cycle in either fed or fasted state until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percentage of AUC 0-∞
C1D1 Number Analyzed 3 participants 12 participants
1.88
(16.2%)
2.11
(50.0%)
C1D15 Number Analyzed 3 participants 12 participants
7.95
(149.3%)
4.28
(85.0%)
C3D1 Number Analyzed 2 participants 10 participants
9.11
(171.3%)
17.56
(50.9%)
44.Secondary Outcome
Title Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily
Hide Description AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: AUCextra = (1- [AUC0-t / AUC0-inf])*100. AUCextra was reported in terms of percentage of AUC0-inf.
Time Frame Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 10 h post-dose on Cycle 1 Day 1 and Day 15; pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8 h post dose on Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PKS analysis set. Here “Number Analyzed” signifies those who were evaluated at the specified time point.
Arm/Group Title MSC1936369B 45 mg MSC1936369B 60 mg MSC1936369B 75 mg
Hide Arm/Group Description:
Subjects received 45 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 60 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received 75 mg of MSC1936369B (capsule formulation) orally, BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 3 18 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage of AUC 0-∞
C1D1 Number Analyzed 3 participants 17 participants 13 participants
16.82
(128.4%)
7.70
(58.3%)
10.90
(68.3%)
C1D15 Number Analyzed 3 participants 18 participants 11 participants
11.78
(42.8%)
14.14
(51.4%)
19.19
(79.3%)
C3D1 Number Analyzed 2 participants 13 participants 6 participants
30.63
(70.7%)
16.43
(37.5%)
21.34
(21.8%)
45.Secondary Outcome
Title Phosphorylated Extra-Cellular Signal-Regulated Kinase (pERK) Fold Change in Peripheral Blood Monocyte Cells (PBMC) and Tot ERK Fold Change in Peripheral Blood Monocyte Cells (PBMC)
Hide Description [Not Specified]
Time Frame Pre-dose on C1D1, C1D2, C1D5, C1D8; 2, 4, 8 h post-dose on C1D1; pre-dose, 2, 8, 24 h post-dose on C1D12-15; pre-dose, 2, 4 h post-dose on C1D3
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included subjects from safety analysis set having at least one pERK/tot ERK sample and not excluded from the analysis as per SAP. Number analyzed= subjects who were evaluated at the specified time point. Data was not available for categories with Number analyzed=0 because there was no subject analyzed at specified time point.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily MSC1936369B Regimen 3 Twice Daily
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Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2.
Subjects received MSC1936369B capsules 60 or 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 41 76 12 31
Mean (Standard Deviation)
Unit of Measure: fold change
C1D1, Pre-dose (pERK) Number Analyzed 41 participants 76 participants 12 participants 31 participants
4.524  (1.839) 3.937  (1.662) 4.121  (1.743) 3.629  (1.491)
C1D1, 2 h post-dose (pERK) Number Analyzed 30 participants 63 participants 12 participants 30 participants
1.235  (0.295) 1.305  (0.755) 1.178  (0.194) 1.249  (0.219)
C1D1, 4 h post-dose (pERK) Number Analyzed 11 participants 13 participants 0 participants 0 participants
3.828  (1.715) 3.422  (1.902)
C1D1, 8 h post-dose (pERK) Number Analyzed 9 participants 39 participants 12 participants 31 participants
1.454  (0.515) 1.454  (0.403) 1.878  (0.836) 1.821  (0.514)
C1D2, Pre-dose (pERK) Number Analyzed 9 participants 40 participants 12 participants 25 participants
2.853  (1.399) 2.411  (1.031) 3.081  (1.249) 2.069  (0.748)
C1D5, Pre-dose (pERK) Number Analyzed 8 participants 0 participants 0 participants 0 participants
2.722  (1.326)
C1D8, Pre-dose (pERK) Number Analyzed 36 participants 69 participants 12 participants 28 participants
4.48  (2.119) 2.868  (1.473) 2.541  (1.338) 2.235  (0.739)
C1D12-15, Pre-dose (pERK) Number Analyzed 37 participants 68 participants 12 participants 28 participants
3.257  (1.671) 3.265  (1.845) 3.241  (2.249) 2.16  (0.814)
C1D12-15, 2 h Post-dose (pERK) Number Analyzed 8 participants 35 participants 12 participants 29 participants
1.252  (0.217) 1.293  (0.447) 1.471  (0.529) 1.315  (0.218)
C1D12-15, 8 h Post-dose (pERK) Number Analyzed 8 participants 35 participants 12 participants 29 participants
1.514  (0.391) 1.653  (0.571) 1.902  (0.87) 1.98  (0.827)
C1D12-15, 24 h Post-dose (pERK) Number Analyzed 6 participants 31 participants 12 participants 20 participants
2.768  (1.594) 2.476  (0.958) 2.598  (1.185) 2.043  (0.76)
C3D1, Pre-dose (pERK) Number Analyzed 16 participants 13 participants 0 participants 0 participants
5.179  (2.151) 3.716  (1.875)
C3D1, 2 h Post-dose (pERK) Number Analyzed 12 participants 4 participants 0 participants 0 participants
1.795  (0.687) 1.288  (0.327)
C3D1, 4 h Post-dose (pERK) Number Analyzed 4 participants 9 participants 0 participants 0 participants
3.106  (0.461) 2.688  (2.065)
C1D1, Pre-dose (Tot ERK) Number Analyzed 40 participants 74 participants 12 participants 31 participants
1.1  (0.468) 1.075  (0.25) 1.02  (0.169) 1.086  (0.277)
C1D1, 2 h post-dose (Tot ERK) Number Analyzed 30 participants 61 participants 12 participants 30 participants
1.063  (0.215) 1.069  (0.247) 1.078  (0.151) 1.079  (0.193)
C1D1, 4 h post-dose (Tot ERK) Number Analyzed 11 participants 13 participants 0 participants 0 participants
1.059  (0.621) 1.012  (0.286)
C1D1, 8 h post-dose (Tot ERK) Number Analyzed 9 participants 37 participants 12 participants 31 participants
1.058  (0.16) 1.095  (0.31) 1.078  (0.143) 1.098  (0.161)
C1D2, Pre-dose (Tot ERK) Number Analyzed 9 participants 38 participants 12 participants 25 participants
1.075  (0.103) 1.13  (0.455) 1.013  (0.273) 1.108  (0.154)
C1D5, Pre-dose (Tot ERK) Number Analyzed 8 participants 0 participants 0 participants 0 participants
1.163  (0.146)
C1D8, Pre-dose (Tot ERK) Number Analyzed 36 participants 67 participants 12 participants 28 participants
1.233  (0.674) 1.108  (0.353) 0.944  (0.117) 1.049  (0.133)
C1D12-15, Pre-dose (Tot ERK) Number Analyzed 37 participants 66 participants 12 participants 28 participants
1.223  (0.476) 1.118  (0.268) 1.333  (0.878) 1.047  (0.144)
C1D12-15, 2 h Post-dose (Tot ERK) Number Analyzed 8 participants 33 participants 12 participants 29 participants
1.04  (0.102) 1.125  (0.34) 1.335  (0.754) 1.059  (0.14)
C1D12-15, 8 h Post-dose (Tot ERK) Number Analyzed 8 participants 33 participants 12 participants 29 participants
0.994  (0.165) 1.041  (0.237) 1.044  (0.238) 1.026  (0.146)
C1D12-15, 24 h Post-dose (Tot ERK) Number Analyzed 6 participants 29 participants 12 participants 20 participants
1.047  (0.153) 1.045  (0.183) 1.048  (0.139) 1.068  (0.141)
C3D1, Pre-dose (Tot ERK) Number Analyzed 16 participants 13 participants 0 participants 0 participants
1.074  (0.34) 1.138  (0.306)
C3D1, 2 h Post-dose (Tot ERK) Number Analyzed 12 participants 4 participants 0 participants 0 participants
1.087  (0.413) 1.251  (0.29)
C3D1, 4 h Post-dose (Tot ERK) Number Analyzed 4 participants 9 participants 0 participants 0 participants
0.674  (0.304) 1.052  (0.182)
46.Secondary Outcome
Title Number of Subjects With Clinical Benefit (Complete Response [CR], Partial Response [PR] or Stable Disease [SD}) and Progressive Disease (PD) Based on the Best Overall Response (BOR)
Hide Description Number of subjects with clinical benefit (CR, PR, or SD) and PD according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) 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 until disease progression (assessed up to end of treatment [253 weeks])
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Hide Analysis Population Description
The SAF included all subjects who received at least 1 administration of MSC1936369B. Here "Number of Subjects analysed" = subjects evaluable for this endpoint.
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 and Regimen 2 Food Effect MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
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Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Combined data for both Regimen 2 with and without food effect was reported in this arm. MSC1936369B Regimen 2: Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (FE): Subjects received MSC1936369B capsules 90-150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Cycle 2 dosing.
Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
Overall Number of Participants Analyzed 39 71 15 33
Measure Type: Number
Unit of Measure: Subjects
CR 0 0 0 1
PR 0 4 2 6
SD 19 34 9 14
PD 20 33 4 12
Time Frame Baseline up to 253 weeks
Adverse Event Reporting Description The safety analysis set (SAF) included all subjects who received at least 1 administration of MSC1936369B.
 
Arm/Group Title MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Hide Arm/Group Description Subjects received MSC1936369B capsules 1 to 120 mg orally, QD on Days 1 to 5, 8 to 12, 15 to 19 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (Without Food Effect): Subjects received MSC1936369B capsules 1 to 255 mg orally QD on Days 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. MSC1936369B Regimen 2 (With Food Effect): Subjects received MSC1936369B capsules 90 or 150 mg orally QD on Day 1 to 15 of each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects in the Regimen 2 FE cohort were assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Day 1 of Cycle 2. Subjects received MSC1936369B capsules 60 to 90 mg orally QD in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision. Subjects received MSC1936369B capsules 45 to 75 mg orally BID in each 21-day treatment cycle until PD or intolerable toxicity or investigator/subject decision.
All-Cause Mortality
MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
MSC1936369B Regimen 1 MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) MSC1936369B Regimen 3 Once Daily (QD) MSC1936369B Regimen 3 Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/49 (46.94%)      45/82 (54.88%)      8/15 (53.33%)      21/34 (61.76%)    
Blood and lymphatic system disorders         
Anaemia * 1  3/49 (6.12%)  3/82 (3.66%)  0/15 (0.00%)  1/34 (2.94%) 
Lymphadenopathy * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Lymphopenia * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Thrombocytopenia * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Neutropenia * 1  0/49 (0.00%)  0/82 (0.00%)  0/15 (0.00%)  1/34 (2.94%) 
Cardiac disorders         
Atrial fibrillation * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Atrial flutter * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Tachycardia * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Bradycardia * 1  0/49 (0.00%)  2/82 (2.44%)  0/15 (0.00%)  0/34 (0.00%) 
Conduction disorder * 1  0/49 (0.00%)  0/82 (0.00%)  0/15 (0.00%)  1/34 (2.94%) 
Sinus bradycardia * 1  0/49 (0.00%)  0/82 (0.00%)  0/15 (0.00%)  1/34 (2.94%) 
Congenital, familial and genetic disorders         
Ichthyosis * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  1/34 (2.94%) 
Eye disorders         
Retinal detachment * 1  2/49 (4.08%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Choroiditis * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Macular degeneration * 1  1/49 (2.04%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Retinal vein occlusion * 1  1/49 (2.04%)  2/82 (2.44%)  0/15 (0.00%)  0/34 (0.00%) 
Retinal vein thrombosis * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Visual acuity reduced * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Visual impairment * 1  0/49 (0.00%)  2/82 (2.44%)  0/15 (0.00%)  0/34 (0.00%) 
Macular oedema * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Retinal haemorrhage * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Vision blurred * 1  0/49 (0.00%)  0/82 (0.00%)  1/15 (6.67%)  0/34 (0.00%) 
Retinal artery occlusion * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  0/34 (0.00%) 
Macular detachment * 1  0/49 (0.00%)  0/82 (0.00%)  0/15 (0.00%)  1/34 (2.94%) 
Gastrointestinal disorders         
Haematemesis * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Subileus * 1  1/49 (2.04%)  0/82 (0.00%)  0/15 (0.00%)  0/34 (0.00%) 
Vomiting * 1  1/49 (2.04%)  2/82 (2.44%)  0/15 (0.00%)  2/34 (5.88%) 
Abdominal pain * 1  0/49 (0.00%)  2/82 (2.44%)  0/15 (0.00%)  1/34 (2.94%) 
Diarrhoea * 1  0/49 (0.00%)  2/82 (2.44%)  2/15 (13.33%)  4/34 (11.76%) 
Stomatitis * 1  0/49 (0.00%)  2/82 (2.44%)  0/15 (0.00%)  1/34 (2.94%) 
Ascites * 1  0/49 (0.00%)  1/82 (1.22%)  0/15 (0.00%)  1/34 (2.94%) 
Constipation * 1  0/49 (0.00%)