Cancer, Solid Tumors
Conditions
Keywords
MEK inhibitor, Cancer, Solid tumors
Brief summary
This is a first in man trial with a primary objective being the determination of the Maximum Tolerated dose (MTD) and the dose-limiting toxicity (DLT) in several regimens of MEK inhibitor MSC1936369B administered orally once a day, in subjects with malignant solid tumors to see how safe is treatment with MSC1936369B.
Interventions
DRUGMSC1936369B
Sponsors
Merck Serono S.A., Geneva
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically-confirmed solid tumor which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available. In the regimen 3, regimen 2 food-effect, and BID cohorts, the tumor type will be restricted to melanoma. * Age greater than or equal to (\>=) 18 years * Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments
Exclusion criteria
* Bone marrow impairment as evidenced by Haemoglobin less than (\<) 9.0 gram per deciliter (g/dL), Neutrophil count \< 1.0\*10\^9/Liter, platelets \< 100\*10\^9/Liter * Renal impairment as evidenced by serum creatinine \> 1.5\*upper limit normal (ULN), and/or calculated creatinine clearance \< 60 milliliter per minute (mL/min) * Liver function abnormality as defined by total bilirubin \> 1.5\*ULN, or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2.5\*ULN, for subjects with liver involvement AST/ALT \> 5\*ULN * INR \> 1.5\*ULN * Serum calcium \> 1\*ULN * History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases, is stable by computer tomography (CT) scan without evidence of cerebral oedema, and has no requirements for corticosteroids or anticonvulsants * History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product * Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than (\>) 1 * Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21 | Day 1 up to Day 21 of Cycle 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death | Baseline up to 253 weeks | — |
| Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Baseline up to 253 weeks | 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. |
| Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | 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 | Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. |
| Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | Cmax was obtained directly from the concentration versus time curve. |
| Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | Cmax was obtained directly from the concentration versus time curve. Summarized data over Day 1 and Day 2 was reported. |
| Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | 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 | Cmax was obtained directly from the concentration versus time curve. |
| Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | 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 | Cmax was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | 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 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | 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 to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | 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 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | 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 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| 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 | 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 | 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. |
| 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) | 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 | 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. |
| 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) | 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 | 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. |
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | 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 | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | 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 | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | 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 | 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. |
| Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | 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 | 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. |
| Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | 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 | 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. |
| Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | 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. |
| Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | 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. |
| Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | 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 | 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. |
| Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | 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 | 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. |
| Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | 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 | 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. |
| Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | 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 | 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. |
| Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect) | 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 | 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. |
| Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | 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 | 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 |
| Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | 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 | 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 |
| Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | 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 | 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. |
| 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) | 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 | 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. |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | Baseline up to 253 weeks | AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 253 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs. |
| Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | 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 | 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. |
| Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | 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 | 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. |
| 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) | 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 | — |
| 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) | Baseline until disease progression (assessed up to end of treatment [253 weeks]) | 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. |
| 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) | 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 | 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. |
Countries
Australia, Belgium, France, Netherlands
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| MSC1936369B Regimen 1 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. | 49 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) 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. | 82 |
| MSC1936369B Regimen 3 Once Daily (QD) 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. | 15 |
| MSC1936369B Regimen 3 Twice Daily 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. | 34 |
| Total | 180 |
Baseline characteristics
| Characteristic | MSC1936369B Regimen 1 | MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | MSC1936369B Regimen 3 Once Daily (QD) | MSC1936369B Regimen 3 Twice Daily | Total |
|---|---|---|---|---|---|
| Age, Customized >= 18 - <45 Years | 4 Participants | 10 Participants | 4 Participants | 7 Participants | 25 Participants |
| Age, Customized >=45 - <65 Years | 30 Participants | 49 Participants | 9 Participants | 13 Participants | 101 Participants |
| Age, Customized >=65 Years | 15 Participants | 23 Participants | 2 Participants | 14 Participants | 54 Participants |
| Sex: Female, Male Female | 20 Participants | 30 Participants | 9 Participants | 11 Participants | 70 Participants |
| Sex: Female, Male Male | 29 Participants | 52 Participants | 6 Participants | 23 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 49 | 80 / 82 | 15 / 15 | 34 / 34 |
| serious Total, serious adverse events | 23 / 49 | 45 / 82 | 8 / 15 | 21 / 34 |
Outcome results
Primary
Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| MSC1936369B Regimen 1 | Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21 | 2 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21 | 6 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21 | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) Over the First Cycle - Day 1 to 21 | 6 Subjects |
Secondary
Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 4.985 Hours (h) | Geometric Coefficient of Variation 123.5 |
| MSC1936369B Regimen 3 Twice Daily | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 3.346 Hours (h) | — |
| MSC1936369B 7 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 9.249 Hours (h) | — |
| MSC1936369B 7 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 3.405 Hours (h) | Geometric Coefficient of Variation 52.1 |
| MSC1936369B 7 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C3D1 | 2.959 Hours (h) | — |
| MSC1936369B 14 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 3.236 Hours (h) | Geometric Coefficient of Variation 19.4 |
| MSC1936369B 14 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 4.599 Hours (h) | Geometric Coefficient of Variation 29.1 |
| MSC1936369B 14 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C3D1 | 2.811 Hours (h) | — |
| MSC1936369B 28 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 6.750 Hours (h) | Geometric Coefficient of Variation 21.5 |
| MSC1936369B 28 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 4.781 Hours (h) | Geometric Coefficient of Variation 39.4 |
| MSC1936369B 45 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 5.389 Hours (h) | Geometric Coefficient of Variation 9.4 |
| MSC1936369B 45 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C3D1 | 2.931 Hours (h) | — |
| MSC1936369B 45 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 4.688 Hours (h) | Geometric Coefficient of Variation 60.4 |
| MSC1936369B 68 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 6.926 Hours (h) | Geometric Coefficient of Variation 33.6 |
| MSC1936369B 68 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 5.335 Hours (h) | Geometric Coefficient of Variation 23.6 |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 5.351 Hours (h) | Geometric Coefficient of Variation 15.9 |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 5.672 Hours (h) | Geometric Coefficient of Variation 15.4 |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C3D1 | 2.842 Hours (h) | — |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D12 | 3.964 Hours (h) | Geometric Coefficient of Variation 44.7 |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C1D1 | 5.247 Hours (h) | Geometric Coefficient of Variation 17.1 |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 1 | C3D1 | 3.038 Hours (h) | Geometric Coefficient of Variation 3.4 |
Secondary
Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: The food effect analysis set (FES). Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 4.898 Hour (h) | Geometric Coefficient of Variation 36.7 |
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 4.534 Hour (h) | Geometric Coefficient of Variation 18.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 4.452 Hour (h) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 6.123 Hour (h) | — |
Secondary
Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.732 Hours (h) | — |
| MSC1936369B Regimen 3 Twice Daily | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2.941 Hours (h) | — |
| MSC1936369B 7 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2.335 Hours (h) | — |
| MSC1936369B 7 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 2.594 Hours (h) | Geometric Coefficient of Variation 5 |
| MSC1936369B 14 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 4.443 Hours (h) | Geometric Coefficient of Variation 67.3 |
| MSC1936369B 14 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 5.119 Hours (h) | Geometric Coefficient of Variation 30.5 |
| MSC1936369B 28 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 5.115 Hours (h) | Geometric Coefficient of Variation 6.6 |
| MSC1936369B 28 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 6.646 Hours (h) | Geometric Coefficient of Variation 19.5 |
| MSC1936369B 45 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 5.277 Hours (h) | Geometric Coefficient of Variation 8 |
| MSC1936369B 45 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4.187 Hours (h) | Geometric Coefficient of Variation 10.3 |
| MSC1936369B 68 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 3.477 Hours (h) | Geometric Coefficient of Variation 11 |
| MSC1936369B 68 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 3.305 Hours (h) | Geometric Coefficient of Variation 84 |
| MSC1936369B 68 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 6.441 Hours (h) | Geometric Coefficient of Variation 28.4 |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 5.193 Hours (h) | Geometric Coefficient of Variation 11.1 |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.853 Hours (h) | — |
| MSC1936369B 94 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4.826 Hours (h) | Geometric Coefficient of Variation 14 |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.863 Hours (h) | Geometric Coefficient of Variation 22 |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 5.057 Hours (h) | Geometric Coefficient of Variation 45.3 |
| MSC1936369B 120 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 4.851 Hours (h) | Geometric Coefficient of Variation 7.9 |
| MSC1936369B 150 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 5.479 Hours (h) | Geometric Coefficient of Variation 14.1 |
| MSC1936369B 150 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4.904 Hours (h) | Geometric Coefficient of Variation 18.8 |
| MSC1936369B 150 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.418 Hours (h) | Geometric Coefficient of Variation 25.2 |
| MSC1936369B 195 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 6.016 Hours (h) | Geometric Coefficient of Variation 18.9 |
| MSC1936369B 195 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 5.641 Hours (h) | Geometric Coefficient of Variation 21.6 |
| MSC1936369B 195 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.628 Hours (h) | Geometric Coefficient of Variation 9.4 |
| MSC1936369B 255 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.260 Hours (h) | Geometric Coefficient of Variation 34.4 |
| MSC1936369B 255 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 4.847 Hours (h) | Geometric Coefficient of Variation 16.4 |
| MSC1936369B 255 mg | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4.313 Hours (h) | Geometric Coefficient of Variation 29.6 |
Secondary
Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 4.236 Hour (h) | Geometric Coefficient of Variation 1.3 |
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 5.259 Hour (h) | Geometric Coefficient of Variation 14.8 |
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 1.780 Hour (h) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 4.097 Hour (h) | Geometric Coefficient of Variation 33.5 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 5.599 Hour (h) | Geometric Coefficient of Variation 30.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 2.680 Hour (h) | Geometric Coefficient of Variation 21.1 |
Secondary
Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 3.144 Hour (h) | — |
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 2.890 Hour (h) | Geometric Coefficient of Variation 23.8 |
| MSC1936369B Regimen 1 | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 2.050 Hour (h) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 2.509 Hour (h) | Geometric Coefficient of Variation 25.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 2.636 Hour (h) | Geometric Coefficient of Variation 17 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 3.265 Hour (h) | Geometric Coefficient of Variation 18.6 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 3.210 Hour (h) | Geometric Coefficient of Variation 23.8 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 2.814 Hour (h) | Geometric Coefficient of Variation 20.2 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Terminal Half-life (t1/2) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 3.260 Hour (h) | Geometric Coefficient of Variation 10.6 |
Secondary
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: The food effect analysis set (FES). Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome Measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 402.4 Liter | Geometric Coefficient of Variation 49 |
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 393.6 Liter | Geometric Coefficient of Variation 40.5 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 288.1 Liter | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 235.2 Liter | — |
Secondary
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 352.10 Liter | — |
| MSC1936369B Regimen 3 Twice Daily | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 252.7 Liter | — |
| MSC1936369B 7 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 454.6 Liter | — |
| MSC1936369B 7 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 339.58 Liter | Geometric Coefficient of Variation 13.2 |
| MSC1936369B 14 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 555.9 Liter | Geometric Coefficient of Variation 84.7 |
| MSC1936369B 14 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 473.32 Liter | Geometric Coefficient of Variation 81.2 |
| MSC1936369B 28 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 319.40 Liter | Geometric Coefficient of Variation 27 |
| MSC1936369B 28 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 432.5 Liter | Geometric Coefficient of Variation 30.7 |
| MSC1936369B 45 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 378.0 Liter | Geometric Coefficient of Variation 23.6 |
| MSC1936369B 45 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 331.36 Liter | Geometric Coefficient of Variation 13.3 |
| MSC1936369B 68 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 206.07 Liter | Geometric Coefficient of Variation 30.5 |
| MSC1936369B 68 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 366.00 Liter | Geometric Coefficient of Variation 22.8 |
| MSC1936369B 68 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 406.6 Liter | Geometric Coefficient of Variation 76.5 |
| MSC1936369B 94 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 385.6 Liter | Geometric Coefficient of Variation 25.9 |
| MSC1936369B 94 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 244.16 Liter | — |
| MSC1936369B 94 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 428.99 Liter | Geometric Coefficient of Variation 22.7 |
| MSC1936369B 120 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 201.39 Liter | Geometric Coefficient of Variation 95.6 |
| MSC1936369B 120 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 361.12 Liter | Geometric Coefficient of Variation 58.1 |
| MSC1936369B 120 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 646.9 Liter | Geometric Coefficient of Variation 96.3 |
| MSC1936369B 150 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 642.1 Liter | Geometric Coefficient of Variation 63.5 |
| MSC1936369B 150 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 463.92 Liter | Geometric Coefficient of Variation 68.7 |
| MSC1936369B 150 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 212.92 Liter | Geometric Coefficient of Variation 34.4 |
| MSC1936369B 195 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 464.2 Liter | Geometric Coefficient of Variation 64.9 |
| MSC1936369B 195 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 440.55 Liter | Geometric Coefficient of Variation 41.7 |
| MSC1936369B 195 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 274.24 Liter | Geometric Coefficient of Variation 53.8 |
| MSC1936369B 255 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 144.24 Liter | Geometric Coefficient of Variation 79.1 |
| MSC1936369B 255 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 295.1 Liter | Geometric Coefficient of Variation 13.4 |
| MSC1936369B 255 mg | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 377.28 Liter | Geometric Coefficient of Variation 42.4 |
Secondary
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 292.61 Liter | Geometric Coefficient of Variation 99 |
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 366.5 Liter | Geometric Coefficient of Variation 131.6 |
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 137.0 Liter | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 336.38 Liter | Geometric Coefficient of Variation 47.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 507.7 Liter | Geometric Coefficient of Variation 66 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 292.5 Liter | Geometric Coefficient of Variation 47.3 |
Secondary
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 571.8 Liter | — |
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 339.51 Liter | — |
| MSC1936369B Regimen 1 | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 297.9 Liter | Geometric Coefficient of Variation 57.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 392.9 Liter | Geometric Coefficient of Variation 81.9 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 292.59 Liter | Geometric Coefficient of Variation 42.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 315.0 Liter | Geometric Coefficient of Variation 59.4 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 362.6 Liter | Geometric Coefficient of Variation 10.2 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 340.43 Liter | Geometric Coefficient of Variation 57.7 |
| MSC1936369B Regimen 3 Once Daily (QD) | Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 437.6 Liter | Geometric Coefficient of Variation 59.1 |
Secondary
Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired 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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 507.8 Liter | Geometric Coefficient of Variation 28.3 |
| MSC1936369B Regimen 3 Twice Daily | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 640.60 Liter | — |
| MSC1936369B 7 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 594.5 Liter | — |
| MSC1936369B 7 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 561.27 Liter | Geometric Coefficient of Variation 12.9 |
| MSC1936369B 7 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C3D1 | 928.91 Liter | — |
| MSC1936369B 14 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 291.9 Liter | Geometric Coefficient of Variation 73 |
| MSC1936369B 14 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 396.76 Liter | Geometric Coefficient of Variation 86.7 |
| MSC1936369B 14 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C3D1 | 422.04 Liter | — |
| MSC1936369B 28 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 365.1 Liter | Geometric Coefficient of Variation 35 |
| MSC1936369B 28 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 336.32 Liter | Geometric Coefficient of Variation 78.8 |
| MSC1936369B 45 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 378.56 Liter | Geometric Coefficient of Variation 23 |
| MSC1936369B 45 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C3D1 | 348.19 Liter | — |
| MSC1936369B 45 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 333.9 Liter | Geometric Coefficient of Variation 65.1 |
| MSC1936369B 68 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 357.8 Liter | Geometric Coefficient of Variation 53.7 |
| MSC1936369B 68 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 307.90 Liter | Geometric Coefficient of Variation 43.1 |
| MSC1936369B 94 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 389.49 Liter | Geometric Coefficient of Variation 28.6 |
| MSC1936369B 94 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 416.3 Liter | Geometric Coefficient of Variation 35.8 |
| MSC1936369B 94 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C3D1 | 438.91 Liter | — |
| MSC1936369B 120 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D12 | 351.4 Liter | Geometric Coefficient of Variation 37.5 |
| MSC1936369B 120 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C1D1 | 361.99 Liter | Geometric Coefficient of Variation 43 |
| MSC1936369B 120 mg | Apparent Volume of Distribution Following Extravascular Administration (Vz/F) of MSC1936369B: Regimen 1 | C3D1 | 316.63 Liter | Geometric Coefficient of Variation 33.9 |
Secondary
Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 81.33 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 21.2 |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 55.15 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 50.60 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 8.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 33.84 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 42.23 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 40.60 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 5.6 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 43.45 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 79.8 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 55.79 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 32.85 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 14.3 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 21.27 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 56.8 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 26.80 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 27.3 |
| MSC1936369B 7 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 19.82 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 37.6 |
| MSC1936369B 7 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 13.08 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 47.7 |
| MSC1936369B 7 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 21.27 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 33.1 |
| MSC1936369B 14 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 15.84 Percentage of AUC 0-∞ | — |
| MSC1936369B 14 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 5.31 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 174.3 |
| MSC1936369B 14 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 7.83 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 193.6 |
| MSC1936369B 28 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 28.06 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 30.6 |
| MSC1936369B 28 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 6.57 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 45 |
| MSC1936369B 28 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 5.39 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 112.5 |
| MSC1936369B 45 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 27.67 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 126 |
| MSC1936369B 45 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 3.52 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 52 |
| MSC1936369B 45 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 8.17 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 29.1 |
| MSC1936369B 68 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 4.08 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 47.3 |
| MSC1936369B 68 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 6.56 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 185.5 |
| MSC1936369B 94 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 4.09 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 75.2 |
| MSC1936369B 94 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 7.94 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 131.8 |
| MSC1936369B 94 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 16.54 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 30.2 |
| MSC1936369B 120 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D12 | 2.97 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 137.2 |
| MSC1936369B 120 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C1D1 | 5.28 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 155.8 |
| MSC1936369B 120 mg | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 1 | C3D1 | 26.05 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 98.7 |
Secondary
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)
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
Population: The food effect analysis set (FES). Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome Measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | Fasted | 2.54 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 149.8 |
| MSC1936369B Regimen 1 | 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) | Fed | 2.21 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 56.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | Fasted | 1.74 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | Fed | 9.96 Percentage of AUC 0-∞ | — |
Secondary
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)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | C1D15 | 40.86 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 2.9 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1 | 33.93 Percentage of AUC 0-∞ | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D15 | 33.34 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 6.4 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1 | 55.78 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 11 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D15 | 35.29 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 30 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1 | 31.63 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 31.2 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C3D1 | 33.77 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 47.7 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D15 | 21.93 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 20.2 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1 | 27.25 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 15.2 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C3D1 | 17.27 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 45 |
| MSC1936369B 7 mg | 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) | C3D1 | 20.68 Percentage of AUC 0-∞ | — |
| MSC1936369B 7 mg | 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) | C1D1 | 15.10 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 63.9 |
| MSC1936369B 7 mg | 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) | C1D15 | 19.45 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 107.4 |
| MSC1936369B 14 mg | 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) | C1D15 | 12.45 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 58 |
| MSC1936369B 14 mg | 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) | C1D1 | 12.17 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 59.8 |
| MSC1936369B 28 mg | 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) | C1D15 | 6.89 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 32.9 |
| MSC1936369B 28 mg | 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) | C1D1 | 3.29 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 3.7 |
| MSC1936369B 28 mg | 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) | C3D1 | 26.32 Percentage of AUC 0-∞ | — |
| MSC1936369B 45 mg | 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) | C1D1 | 1.46 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 30.8 |
| MSC1936369B 45 mg | 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) | C1D15 | 2.96 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 1.9 |
| MSC1936369B 68 mg | 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) | C1D1 | 2.66 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 40.8 |
| MSC1936369B 68 mg | 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) | C1D15 | 5.00 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 141.4 |
| MSC1936369B 68 mg | 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) | C3D1 | 15.35 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 29.7 |
| MSC1936369B 94 mg | 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) | C3D1 | 18.02 Percentage of AUC 0-∞ | — |
| MSC1936369B 94 mg | 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) | C1D1 | 2.60 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 33.4 |
| MSC1936369B 94 mg | 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) | C1D15 | 3.40 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 33.9 |
| MSC1936369B 120 mg | 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) | C3D1 | 16.22 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 26.9 |
| MSC1936369B 120 mg | 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) | C1D15 | 5.82 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 251.8 |
| MSC1936369B 120 mg | 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) | C1D1 | 2.94 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 181 |
| MSC1936369B 150 mg | 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) | C3D1 | 17.54 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 83.4 |
| MSC1936369B 150 mg | 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) | C1D1 | 2.64 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 68.3 |
| MSC1936369B 150 mg | 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) | C1D15 | 4.82 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 82.9 |
| MSC1936369B 195 mg | 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) | C1D1 | 4.36 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 76.2 |
| MSC1936369B 195 mg | 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) | C1D15 | 5.77 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 72.8 |
| MSC1936369B 195 mg | 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) | C3D1 | 23.45 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 59.4 |
| MSC1936369B 255 mg | 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) | C1D15 | 5.22 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 112.2 |
| MSC1936369B 255 mg | 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) | C1D1 | 3.57 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 149.3 |
| MSC1936369B 255 mg | 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) | C3D1 | 11.15 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 77.4 |
Secondary
Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C1D1 | 1.88 percentage of AUC 0-∞ | Geometric Coefficient of Variation 16.2 |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C1D15 | 7.95 percentage of AUC 0-∞ | Geometric Coefficient of Variation 149.3 |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C3D1 | 9.11 percentage of AUC 0-∞ | Geometric Coefficient of Variation 171.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C1D1 | 2.11 percentage of AUC 0-∞ | Geometric Coefficient of Variation 50 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C1D15 | 4.28 percentage of AUC 0-∞ | Geometric Coefficient of Variation 85 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Once Daily | C3D1 | 17.56 percentage of AUC 0-∞ | Geometric Coefficient of Variation 50.9 |
Secondary
Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D15 | 11.78 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 42.8 |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D1 | 16.82 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 128.4 |
| MSC1936369B Regimen 1 | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C3D1 | 30.63 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 70.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D15 | 14.14 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 51.4 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D1 | 7.70 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 58.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C3D1 | 16.43 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 37.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D1 | 10.90 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 68.3 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C3D1 | 21.34 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 21.8 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Concentration Time Curve Extrapolated From Last Observation to Infinity Given as Percentage of AUC 0-∞ (AUC Extra): Regimen 3 Twice Daily | C1D15 | 19.19 Percentage of AUC 0-∞ | Geometric Coefficient of Variation 79.3 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 136.2 hour*ng/mL | Geometric Coefficient of Variation 9.2 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 15.4 hour*ng/mL | — |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 38.3 hour*ng/mL | Geometric Coefficient of Variation 254.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 9.4 hour*ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 6.2 hour*ng/mL | — |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 43.8 hour*ng/mL | Geometric Coefficient of Variation 58.7 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 55.5 hour*ng/mL | Geometric Coefficient of Variation 321.8 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 47.6 hour*ng/mL | — |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 34.4 hour*ng/mL | Geometric Coefficient of Variation 37.6 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 47.5 hour*ng/mL | Geometric Coefficient of Variation 68.1 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 31.4 hour*ng/mL | Geometric Coefficient of Variation 29.7 |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 105.6 hour*ng/mL | Geometric Coefficient of Variation 57.6 |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 61.3 hour*ng/mL | Geometric Coefficient of Variation 66.9 |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 55.5 hour*ng/mL | Geometric Coefficient of Variation 90 |
| MSC1936369B 14 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 134.5 hour*ng/mL | — |
| MSC1936369B 14 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 234.1 hour*ng/mL | Geometric Coefficient of Variation 70.2 |
| MSC1936369B 14 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 206.3 hour*ng/mL | Geometric Coefficient of Variation 106.5 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 489.8 hour*ng/mL | Geometric Coefficient of Variation 55.2 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 805.6 hour*ng/mL | Geometric Coefficient of Variation 58.9 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 574.2 hour*ng/mL | Geometric Coefficient of Variation 50 |
| MSC1936369B 45 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 1072.1 hour*ng/mL | Geometric Coefficient of Variation 121.6 |
| MSC1936369B 45 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 924.2 hour*ng/mL | Geometric Coefficient of Variation 32.7 |
| MSC1936369B 45 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 960.7 hour*ng/mL | Geometric Coefficient of Variation 46.9 |
| MSC1936369B 68 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 1699.7 hour*ng/mL | Geometric Coefficient of Variation 36.1 |
| MSC1936369B 68 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 2108.2 hour*ng/mL | Geometric Coefficient of Variation 115 |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 1836.4 hour*ng/mL | Geometric Coefficient of Variation 42.8 |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 2257.6 hour*ng/mL | Geometric Coefficient of Variation 30.1 |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 1056.0 hour*ng/mL | Geometric Coefficient of Variation 26.6 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D12 | 2022.8 hour*ng/mL | Geometric Coefficient of Variation 41.3 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C1D1 | 2773.5 hour*ng/mL | Geometric Coefficient of Variation 54.7 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B : Regimen 1 | C3D1 | 3477.6 hour*ng/mL | Geometric Coefficient of Variation 102 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: The food effect analysis set (FES). Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 1580.6 hour*ng/mL | Geometric Coefficient of Variation 48.7 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 1495.7 hour*ng/mL | Geometric Coefficient of Variation 41.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 3344.3 hour*ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 5633.8 hour*ng/mL | — |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 15.7 hour*ng/mL | Geometric Coefficient of Variation 10.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 15.4 hour*ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 33.3 hour*ng/mL | Geometric Coefficient of Variation 45.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 23.4 hour*ng/mL | Geometric Coefficient of Variation 65.7 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 21.9 hour*ng/mL | Geometric Coefficient of Variation 91.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 23.6 hour*ng/mL | Geometric Coefficient of Variation 22.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 41.2 hour*ng/mL | Geometric Coefficient of Variation 41.4 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 102.0 hour*ng/mL | Geometric Coefficient of Variation 63.6 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 59.1 hour*ng/mL | Geometric Coefficient of Variation 6.2 |
| MSC1936369B Regimen 3 Twice Daily | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 49.5 hour*ng/mL | Geometric Coefficient of Variation 17.4 |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 58.1 hour*ng/mL | — |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 90.3 hour*ng/mL | Geometric Coefficient of Variation 30.8 |
| MSC1936369B 7 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 89.7 hour*ng/mL | Geometric Coefficient of Variation 85.9 |
| MSC1936369B 14 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 172.2 hour*ng/mL | Geometric Coefficient of Variation 9 |
| MSC1936369B 14 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 218.4 hour*ng/mL | Geometric Coefficient of Variation 62.1 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 669.1 hour*ng/mL | Geometric Coefficient of Variation 10.5 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 646.9 hour*ng/mL | Geometric Coefficient of Variation 20.7 |
| MSC1936369B 28 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 415.6 hour*ng/mL | — |
| MSC1936369B 45 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 820.4 hour*ng/mL | Geometric Coefficient of Variation 15.7 |
| MSC1936369B 45 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 933.9 hour*ng/mL | Geometric Coefficient of Variation 15.4 |
| MSC1936369B 68 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 885.8 hour*ng/mL | Geometric Coefficient of Variation 111 |
| MSC1936369B 68 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1665.2 hour*ng/mL | Geometric Coefficient of Variation 132.1 |
| MSC1936369B 68 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1655.1 hour*ng/mL | Geometric Coefficient of Variation 19.1 |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1584.8 hour*ng/mL | — |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1525.6 hour*ng/mL | Geometric Coefficient of Variation 13.2 |
| MSC1936369B 94 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1893.2 hour*ng/mL | Geometric Coefficient of Variation 17.5 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2461.3 hour*ng/mL | Geometric Coefficient of Variation 64.3 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2129.0 hour*ng/mL | Geometric Coefficient of Variation 123.7 |
| MSC1936369B 120 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 2424.2 hour*ng/mL | Geometric Coefficient of Variation 109.7 |
| MSC1936369B 150 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2796.2 hour*ng/mL | Geometric Coefficient of Variation 59.3 |
| MSC1936369B 150 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 2287.8 hour*ng/mL | Geometric Coefficient of Variation 77.4 |
| MSC1936369B 150 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2029.9 hour*ng/mL | Geometric Coefficient of Variation 63.3 |
| MSC1936369B 195 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 3602.2 hour*ng/mL | Geometric Coefficient of Variation 46.2 |
| MSC1936369B 195 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 3900.8 hour*ng/mL | Geometric Coefficient of Variation 64.3 |
| MSC1936369B 195 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 3452.9 hour*ng/mL | Geometric Coefficient of Variation 61.6 |
| MSC1936369B 255 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 6232.1 hour*ng/mL | Geometric Coefficient of Variation 7 |
| MSC1936369B 255 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4300.3 hour*ng/mL | Geometric Coefficient of Variation 54.2 |
| MSC1936369B 255 mg | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 5651.1 hour*ng/mL | Geometric Coefficient of Variation 23.5 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 1253.1 hour*ng/mL | Geometric Coefficient of Variation 96.9 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 1753.9 hour*ng/mL | Geometric Coefficient of Variation 93.1 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 1597.0 hour*ng/mL | Geometric Coefficient of Variation 50.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 1581.4 hour*ng/mL | Geometric Coefficient of Variation 56.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 1517.1 hour*ng/mL | Geometric Coefficient of Variation 65.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 1400.3 hour*ng/mL | Geometric Coefficient of Variation 53 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 674.1 hour*ng/mL | Geometric Coefficient of Variation 73.6 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 527.6 hour*ng/mL | Geometric Coefficient of Variation 57.4 |
| MSC1936369B Regimen 1 | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 696.0 hour*ng/mL | Geometric Coefficient of Variation 101.4 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 1004.2 hour*ng/mL | Geometric Coefficient of Variation 46.4 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 742.3 hour*ng/mL | Geometric Coefficient of Variation 47.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 700.8 hour*ng/mL | Geometric Coefficient of Variation 79 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 939.9 hour*ng/mL | Geometric Coefficient of Variation 67.3 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 1285.7 hour*ng/mL | Geometric Coefficient of Variation 29 |
| MSC1936369B Regimen 3 Once Daily (QD) | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 978.4 hour*ng/mL | Geometric Coefficient of Variation 63.7 |
Secondary
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
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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 | C1D12 | 7.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 269.8 |
| MSC1936369B Regimen 1 | 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 | C1D1 | 4.6 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 431.3 |
| MSC1936369B Regimen 1 | 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 | C3D1 | 6.9 hour*nanogram per milliliter (h*ng/mL) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C3D1 | 2.7 hour*nanogram per milliliter (h*ng/mL) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D1 | 5.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 63.9 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D12 | 6.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 89.3 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C1D1 | 18.5 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 49.8 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C1D12 | 26.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C3D1 | 21.0 hour*nanogram per milliliter (h*ng/mL) | — |
| MSC1936369B Regimen 3 Twice Daily | 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 | C3D1 | 23.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 38.2 |
| MSC1936369B Regimen 3 Twice Daily | 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 | C1D12 | 35.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 79.7 |
| MSC1936369B Regimen 3 Twice Daily | 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 | C1D1 | 22.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 29.2 |
| MSC1936369B 7 mg | 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 | C1D1 | 52.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 74.5 |
| MSC1936369B 7 mg | 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 | C1D12 | 83.6 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 67.7 |
| MSC1936369B 7 mg | 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 | C3D1 | 45.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 51.8 |
| MSC1936369B 14 mg | 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 | C1D1 | 213.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 84 |
| MSC1936369B 14 mg | 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 | C1D12 | 182.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 125.1 |
| MSC1936369B 14 mg | 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 | C3D1 | 113.2 hour*nanogram per milliliter (h*ng/mL) | — |
| MSC1936369B 28 mg | 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 | C3D1 | 334.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.8 |
| MSC1936369B 28 mg | 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 | C1D12 | 691.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 51.4 |
| MSC1936369B 28 mg | 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 | C1D1 | 531.3 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.4 |
| MSC1936369B 45 mg | 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 | C3D1 | 666.3 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 52.3 |
| MSC1936369B 45 mg | 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 | C1D12 | 880.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 45.7 |
| MSC1936369B 45 mg | 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 | C1D1 | 889.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.9 |
| MSC1936369B 68 mg | 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 | C1D12 | 1900.3 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 99.7 |
| MSC1936369B 68 mg | 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 | C1D1 | 1624.8 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.1 |
| MSC1936369B 94 mg | 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 | C1D12 | 1991.4 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.2 |
| MSC1936369B 94 mg | 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 | C1D1 | 1748.1 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 38.8 |
| MSC1936369B 94 mg | 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 | C3D1 | 876.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.4 |
| MSC1936369B 120 mg | 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 | C1D12 | 1682.4 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 52.4 |
| MSC1936369B 120 mg | 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 | C1D1 | 2292.4 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 52.5 |
| MSC1936369B 120 mg | 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 | C3D1 | 2064.1 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55 |
Secondary
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)
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
Population: The food effect analysis set (FES). Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | Fasted | 1509.6 hour*ng/mL | Geometric Coefficient of Variation 46.6 |
| MSC1936369B Regimen 1 | 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) | Fed | 1458.3 hour*ng/mL | Geometric Coefficient of Variation 41.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | Fasted | 3286 hour*ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | Fed | 5072.9 hour*ng/mL | — |
Secondary
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)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | C1D1 | 1.9 hour*ng/mL | Geometric Coefficient of Variation 331.6 |
| MSC1936369B Regimen 1 | 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) | C3D1 | 0.5 hour*ng/mL | Geometric Coefficient of Variation 76.6 |
| MSC1936369B Regimen 1 | 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) | C1D15 | 4.3 hour*ng/mL | Geometric Coefficient of Variation 228.5 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1 | 8.2 hour*ng/mL | Geometric Coefficient of Variation 53.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1 | 10.2 hour*ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D15 | 22.2 hour*ng/mL | Geometric Coefficient of Variation 42.1 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1 | 6.7 hour*ng/mL | Geometric Coefficient of Variation 292.9 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D15 | 13.8 hour*ng/mL | Geometric Coefficient of Variation 66.9 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C3D1 | 26.2 hour*ng/mL | Geometric Coefficient of Variation 15.6 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C3D1 | 40.5 hour*ng/mL | Geometric Coefficient of Variation 26.9 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1 | 67.9 hour*ng/mL | Geometric Coefficient of Variation 93.9 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D15 | 79.3 hour*ng/mL | Geometric Coefficient of Variation 57.9 |
| MSC1936369B 7 mg | 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) | C3D1 | 46.1 hour*ng/mL | — |
| MSC1936369B 7 mg | 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) | C1D1 | 74.4 hour*ng/mL | Geometric Coefficient of Variation 19.4 |
| MSC1936369B 7 mg | 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) | C1D15 | 67.8 hour*ng/mL | Geometric Coefficient of Variation 53.9 |
| MSC1936369B 14 mg | 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) | C1D15 | 161.5 hour*ng/mL | Geometric Coefficient of Variation 14.1 |
| MSC1936369B 14 mg | 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) | C1D1 | 188.4 hour*ng/mL | Geometric Coefficient of Variation 61.7 |
| MSC1936369B 28 mg | 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) | C1D15 | 621.2 hour*ng/mL | Geometric Coefficient of Variation 12.7 |
| MSC1936369B 28 mg | 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) | C1D1 | 625.7 hour*ng/mL | Geometric Coefficient of Variation 20.6 |
| MSC1936369B 28 mg | 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) | C3D1 | 306.2 hour*ng/mL | — |
| MSC1936369B 45 mg | 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) | C1D1 | 808.0 hour*ng/mL | Geometric Coefficient of Variation 15.7 |
| MSC1936369B 45 mg | 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) | C1D15 | 906.3 hour*ng/mL | Geometric Coefficient of Variation 15.4 |
| MSC1936369B 68 mg | 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) | C1D1 | 861.1 hour*ng/mL | Geometric Coefficient of Variation 112.4 |
| MSC1936369B 68 mg | 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) | C1D15 | 1553.9 hour*ng/mL | Geometric Coefficient of Variation 122.5 |
| MSC1936369B 68 mg | 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) | C3D1 | 1394.7 hour*ng/mL | Geometric Coefficient of Variation 24.6 |
| MSC1936369B 94 mg | 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) | C1D1 | 1484.6 hour*ng/mL | Geometric Coefficient of Variation 13 |
| MSC1936369B 94 mg | 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) | C1D15 | 1826.2 hour*ng/mL | Geometric Coefficient of Variation 17.9 |
| MSC1936369B 94 mg | 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) | C3D1 | 1299.3 hour*ng/mL | — |
| MSC1936369B 120 mg | 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) | C3D1 | 2053.6 hour*ng/mL | Geometric Coefficient of Variation 71.1 |
| MSC1936369B 120 mg | 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) | C1D15 | 1862.3 hour*ng/mL | Geometric Coefficient of Variation 96.4 |
| MSC1936369B 120 mg | 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) | C1D1 | 2287.0 hour*ng/mL | Geometric Coefficient of Variation 96.6 |
| MSC1936369B 150 mg | 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) | C1D1 | 2216.5 hour*ng/mL | Geometric Coefficient of Variation 75.7 |
| MSC1936369B 150 mg | 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) | C3D1 | 2171.2 hour*ng/mL | Geometric Coefficient of Variation 59.4 |
| MSC1936369B 150 mg | 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) | C1D15 | 2086.6 hour*ng/mL | Geometric Coefficient of Variation 69.9 |
| MSC1936369B 195 mg | 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) | C1D1 | 3415.6 hour*ng/mL | Geometric Coefficient of Variation 44.5 |
| MSC1936369B 195 mg | 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) | C1D15 | 3436.8 hour*ng/mL | Geometric Coefficient of Variation 64.7 |
| MSC1936369B 195 mg | 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) | C3D1 | 2484.5 hour*ng/mL | Geometric Coefficient of Variation 53.6 |
| MSC1936369B 255 mg | 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) | C1D15 | 5765.9 hour*ng/mL | Geometric Coefficient of Variation 15.3 |
| MSC1936369B 255 mg | 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) | C1D1 | 4041.3 hour*ng/mL | Geometric Coefficient of Variation 60.8 |
| MSC1936369B 255 mg | 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) | C3D1 | 4906.3 hour*ng/mL | Geometric Coefficient of Variation 19.2 |
Secondary
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
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
Population: PKS analysis set. Here Number analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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 | C1D1 | 1229.3 hour*ng/mL | Geometric Coefficient of Variation 96.5 |
| MSC1936369B Regimen 1 | 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 | C1D15 | 1532.4 hour*ng/mL | Geometric Coefficient of Variation 80.4 |
| MSC1936369B Regimen 1 | 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 | C3D1 | 1392.3 hour*ng/mL | Geometric Coefficient of Variation 35.2 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D1 | 1544.9 hour*ng/mL | Geometric Coefficient of Variation 57.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D15 | 1428.8 hour*ng/mL | Geometric Coefficient of Variation 63.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C3D1 | 1122.5 hour*ng/mL | Geometric Coefficient of Variation 45.2 |
Secondary
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
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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 | C3D1 | 450.0 hour*ng/mL | Geometric Coefficient of Variation 57.1 |
| MSC1936369B Regimen 1 | 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 | C1D15 | 589.3 hour*ng/mL | Geometric Coefficient of Variation 66.5 |
| MSC1936369B Regimen 1 | 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 | C1D1 | 407.2 hour*ng/mL | Geometric Coefficient of Variation 40.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C3D1 | 577.0 hour*ng/mL | Geometric Coefficient of Variation 72.5 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D1 | 681.4 hour*ng/mL | Geometric Coefficient of Variation 43.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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 | C1D15 | 838.8 hour*ng/mL | Geometric Coefficient of Variation 43.9 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C3D1 | 1005.0 hour*ng/mL | Geometric Coefficient of Variation 25.6 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C1D15 | 710.3 hour*ng/mL | Geometric Coefficient of Variation 65 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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 | C1D1 | 791.1 hour*ng/mL | Geometric Coefficient of Variation 62.3 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1
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
Population: 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 \& 0indicates no subject analyzed for that specific time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 2.92 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 2.02 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 2.00 nanogram per milliliter (ng/mL) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 2.69 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 10.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 2.90 nanogram per milliliter (ng/mL) | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 3.20 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 5.60 nanogram per milliliter (ng/mL) | — |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 6.29 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.6 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 4.21 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47.9 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 9.75 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.3 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 6.69 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 62.9 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 8.06 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30.3 |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 10.90 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 68.5 |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 12.60 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.4 |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 21.93 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 110.5 |
| MSC1936369B 14 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 54.47 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 116.2 |
| MSC1936369B 14 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 62.32 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33.6 |
| MSC1936369B 14 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 51.30 nanogram per milliliter (ng/mL) | — |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 126.21 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 70.2 |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 150.67 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 78.1 |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 84.70 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 78.8 |
| MSC1936369B 45 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 212.96 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 106.3 |
| MSC1936369B 45 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 175.94 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47.5 |
| MSC1936369B 45 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 167.75 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.5 |
| MSC1936369B 68 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 413.58 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 9.1 |
| MSC1936369B 68 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 357.39 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30.7 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 602.12 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 11 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 325.99 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31.8 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 282.44 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14.9 |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C3D1 | 652.70 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48.3 |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D1 | 428.85 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 57.9 |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 1 | C1D12 | 425.26 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 321.14 ng/mL | Geometric Coefficient of Variation 58.3 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 305.94 ng/mL | Geometric Coefficient of Variation 45.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 1158.00 ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 370.70 ng/mL | — |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.65 ng/mL | Geometric Coefficient of Variation 59.2 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.25 ng/mL | Geometric Coefficient of Variation 5.7 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2.28 ng/mL | Geometric Coefficient of Variation 58 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 2.87 ng/mL | Geometric Coefficient of Variation 56.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 4.30 ng/mL | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 7.77 ng/mL | Geometric Coefficient of Variation 96.2 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 4.55 ng/mL | Geometric Coefficient of Variation 113.4 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 4.21 ng/mL | Geometric Coefficient of Variation 39.9 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 6.56 ng/mL | Geometric Coefficient of Variation 39.8 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 14.81 ng/mL | Geometric Coefficient of Variation 50.1 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 17.26 ng/mL | Geometric Coefficient of Variation 27.8 |
| MSC1936369B Regimen 3 Twice Daily | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 18.78 ng/mL | Geometric Coefficient of Variation 32.2 |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 16.10 ng/mL | — |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 30.90 ng/mL | Geometric Coefficient of Variation 32.6 |
| MSC1936369B 7 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 18.47 ng/mL | Geometric Coefficient of Variation 33.1 |
| MSC1936369B 14 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 34.87 ng/mL | Geometric Coefficient of Variation 36.8 |
| MSC1936369B 14 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 39.19 ng/mL | Geometric Coefficient of Variation 69.7 |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 131.71 ng/mL | Geometric Coefficient of Variation 14.7 |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 187.98 ng/mL | Geometric Coefficient of Variation 39.7 |
| MSC1936369B 28 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 96.60 ng/mL | — |
| MSC1936369B 45 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 321.85 ng/mL | Geometric Coefficient of Variation 32.7 |
| MSC1936369B 45 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 286.88 ng/mL | Geometric Coefficient of Variation 21.8 |
| MSC1936369B 68 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 306.63 ng/mL | Geometric Coefficient of Variation 110.4 |
| MSC1936369B 68 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 539.17 ng/mL | Geometric Coefficient of Variation 37.1 |
| MSC1936369B 68 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 710.94 ng/mL | Geometric Coefficient of Variation 57.4 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 373.59 ng/mL | Geometric Coefficient of Variation 24.9 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 432.46 ng/mL | Geometric Coefficient of Variation 7.6 |
| MSC1936369B 94 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 532.80 ng/mL | — |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 568.49 ng/mL | Geometric Coefficient of Variation 76.2 |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 492.81 ng/mL | Geometric Coefficient of Variation 117.1 |
| MSC1936369B 120 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 605.11 ng/mL | Geometric Coefficient of Variation 48.8 |
| MSC1936369B 150 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 539.02 ng/mL | Geometric Coefficient of Variation 78 |
| MSC1936369B 150 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 795.86 ng/mL | Geometric Coefficient of Variation 50 |
| MSC1936369B 150 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 450.29 ng/mL | Geometric Coefficient of Variation 67.4 |
| MSC1936369B 195 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 680.87 ng/mL | Geometric Coefficient of Variation 45.6 |
| MSC1936369B 195 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 629.85 ng/mL | Geometric Coefficient of Variation 71.3 |
| MSC1936369B 195 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 773.14 ng/mL | Geometric Coefficient of Variation 51 |
| MSC1936369B 255 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1535.60 ng/mL | Geometric Coefficient of Variation 57.1 |
| MSC1936369B 255 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 990.92 ng/mL | Geometric Coefficient of Variation 64.9 |
| MSC1936369B 255 mg | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2344.91 ng/mL | Geometric Coefficient of Variation 23.1 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies the subjects who were evaluated at that specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 241.27 ng/mL | Geometric Coefficient of Variation 47 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 316.08 ng/mL | Geometric Coefficient of Variation 34.9 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 473.27 ng/mL | Geometric Coefficient of Variation 38.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 402.77 ng/mL | Geometric Coefficient of Variation 59.2 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 324.80 ng/mL | Geometric Coefficient of Variation 65.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 376.62 ng/mL | Geometric Coefficient of Variation 45.2 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily
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
Population: PKS analysis set. Here Number analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 178.09 ng/mL | Geometric Coefficient of Variation 95 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 132.57 ng/mL | Geometric Coefficient of Variation 40.2 |
| MSC1936369B Regimen 1 | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 139.60 ng/mL | Geometric Coefficient of Variation 26.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 231.12 ng/mL | Geometric Coefficient of Variation 44 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 206.46 ng/mL | Geometric Coefficient of Variation 41.7 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 157.46 ng/mL | Geometric Coefficient of Variation 53.7 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 263.08 ng/mL | Geometric Coefficient of Variation 68.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 329.28 ng/mL | Geometric Coefficient of Variation 73.5 |
| MSC1936369B Regimen 3 Once Daily (QD) | Maximum Observed Plasma Concentration (Cmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 190.42 ng/mL | Geometric Coefficient of Variation 57.6 |
Secondary
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)
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])
Population: The SAF included all subjects who received at least 1 administration of MSC1936369B. Here Number of Subjects analysed = subjects evaluable for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | CR | 0 Subjects |
| MSC1936369B Regimen 1 | 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) | PR | 0 Subjects |
| MSC1936369B Regimen 1 | 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) | SD | 19 Subjects |
| MSC1936369B Regimen 1 | 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) | PD | 20 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | PR | 4 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | SD | 34 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | PD | 33 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | CR | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | SD | 9 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | PR | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | PD | 4 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | CR | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | 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) | PD | 12 Subjects |
| MSC1936369B Regimen 3 Twice Daily | 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) | PR | 6 Subjects |
| MSC1936369B Regimen 3 Twice Daily | 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) | CR | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | 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) | SD | 14 Subjects |
Secondary
Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events
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
Population: SAF analysis was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperkalaemia | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Haemoglobin decreased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Anaemia | 10 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Lymphopenia | 3 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Thrombocytopenia | 3 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Platelet count decreased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Neutropenia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Leukopenia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Pancytopenia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyponatraemia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypokalaemia | 4 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypocalcaemia | 2 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypercalcaemia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypomagnesaemia | 2 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypophosphataemia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic enzyme increased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic function abnormal | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Alanine aminotransferase increased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Aspartate aminotransferase increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood alkaline phosphatase increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperbilirubinaemia | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood lactate dehydrogenase increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatine phosphokinase increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatinine increased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood 25-hydroxycholecalciferol decreased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Vitamin D decreased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood parathyroid hormone increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperglycaemia | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | C-reactive protein increased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Proteinuria | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthyroidism | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypoalbuminaemia | 3 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight increased | 0 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight decreased | 6 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthermia | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypertension | 7 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypotension | 3 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Heart rate increased | 1 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Tachycardia | 3 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood potassium increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Proteinuria | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperbilirubinaemia | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight increased | 3 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Heart rate increased | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypertension | 5 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood lactate dehydrogenase increased | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Platelet count decreased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | C-reactive protein increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypocalcaemia | 7 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatine phosphokinase increased | 2 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypophosphataemia | 2 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood potassium increased | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperglycaemia | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatinine increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperkalaemia | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood parathyroid hormone increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Vitamin D decreased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood 25-hydroxycholecalciferol decreased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypoalbuminaemia | 4 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypotension | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Thrombocytopenia | 6 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic enzyme increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Leukopenia | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Lymphopenia | 7 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Tachycardia | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic function abnormal | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypercalcaemia | 3 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Anaemia | 23 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthermia | 5 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Alanine aminotransferase increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyponatraemia | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Haemoglobin decreased | 2 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Neutropenia | 4 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Aspartate aminotransferase increased | 1 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight decreased | 8 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthyroidism | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypokalaemia | 10 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood alkaline phosphatase increased | 0 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypomagnesaemia | 3 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Pancytopenia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypoalbuminaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperkalaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypocalcaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypercalcaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypomagnesaemia | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight decreased | 4 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypophosphataemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic enzyme increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Tachycardia | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic function abnormal | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Alanine aminotransferase increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthermia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Aspartate aminotransferase increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood alkaline phosphatase increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperbilirubinaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood lactate dehydrogenase increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypertension | 1 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatine phosphokinase increased | 1 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatinine increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood 25-hydroxycholecalciferol decreased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Vitamin D decreased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypotension | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood parathyroid hormone increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperglycaemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | C-reactive protein increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Proteinuria | 1 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Heart rate increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Pancytopenia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypokalaemia | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Haemoglobin decreased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthyroidism | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Anaemia | 3 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Lymphopenia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Thrombocytopenia | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Platelet count decreased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Neutropenia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Leukopenia | 1 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood potassium increased | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyponatraemia | 0 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperkalaemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood alkaline phosphatase increased | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Neutropenia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthermia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypoalbuminaemia | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Aspartate aminotransferase increased | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Alanine aminotransferase increased | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypocalcaemia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypokalaemia | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic function abnormal | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Leukopenia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Anaemia | 3 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperthyroidism | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hepatic enzyme increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyponatraemia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Lymphopenia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Heart rate increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight decreased | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Pancytopenia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Thrombocytopenia | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood 25-hydroxycholecalciferol decreased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood potassium increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypophosphataemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Vitamin D decreased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypomagnesaemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatinine increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Weight increased | 3 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood parathyroid hormone increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypotension | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypertension | 4 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Platelet count decreased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperglycaemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood creatine phosphokinase increased | 5 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Blood lactate dehydrogenase increased | 1 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Haemoglobin decreased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | C-reactive protein increased | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hyperbilirubinaemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Tachycardia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Hypercalcaemia | 0 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Clinical Significant Laboratory Abnormalities and Vital Signs Reported as Treatment Emergent Adverse Events | Proteinuria | 1 Subjects |
Secondary
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation
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
Population: Safety Analysis Set (SAF) included all subjects who received at least 1 dose of MSC1936369B treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 13 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 47 Subjects |
| MSC1936369B Regimen 1 | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 23 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 45 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 82 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 22 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 2 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 15 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 8 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 21 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 34 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 6 Subjects |
Secondary
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death
Time frame: Baseline up to 253 weeks
Population: ALL subject analysis set was used which included all the subjects who signed the informed consent form and entered the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MSC1936369B Regimen 1 | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death | 10 Subjects |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death | 14 Subjects |
| MSC1936369B Regimen 3 Once Daily (QD) | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death | 2 Subjects |
| MSC1936369B Regimen 3 Twice Daily | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Death | 2 Subjects |
Secondary
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)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | 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) | C1D12-15, 24 h Post-dose (Tot ERK) | 1.047 fold change | Standard Deviation 0.153 |
| MSC1936369B Regimen 1 | 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) | C1D1, 2 h post-dose (Tot ERK) | 1.063 fold change | Standard Deviation 0.215 |
| MSC1936369B Regimen 1 | 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) | C1D1, Pre-dose (Tot ERK) | 1.1 fold change | Standard Deviation 0.468 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, 8 h Post-dose (pERK) | 1.514 fold change | Standard Deviation 0.391 |
| MSC1936369B Regimen 1 | 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) | C1D1, 4 h post-dose (pERK) | 3.828 fold change | Standard Deviation 1.715 |
| MSC1936369B Regimen 1 | 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) | C3D1, 4 h Post-dose (pERK) | 3.106 fold change | Standard Deviation 0.461 |
| MSC1936369B Regimen 1 | 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) | C3D1, 2 h Post-dose (pERK) | 1.795 fold change | Standard Deviation 0.687 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, 24 h Post-dose (pERK) | 2.768 fold change | Standard Deviation 1.594 |
| MSC1936369B Regimen 1 | 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) | C3D1, 2 h Post-dose (Tot ERK) | 1.087 fold change | Standard Deviation 0.413 |
| MSC1936369B Regimen 1 | 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) | C3D1, Pre-dose (pERK) | 5.179 fold change | Standard Deviation 2.151 |
| MSC1936369B Regimen 1 | 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) | C1D1, 8 h post-dose (pERK) | 1.454 fold change | Standard Deviation 0.515 |
| MSC1936369B Regimen 1 | 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) | C1D1, Pre-dose (pERK) | 4.524 fold change | Standard Deviation 1.839 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, 8 h Post-dose (Tot ERK) | 0.994 fold change | Standard Deviation 0.165 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, 2 h Post-dose (Tot ERK) | 1.04 fold change | Standard Deviation 0.102 |
| MSC1936369B Regimen 1 | 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) | C1D2, Pre-dose (pERK) | 2.853 fold change | Standard Deviation 1.399 |
| MSC1936369B Regimen 1 | 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) | C1D1, 2 h post-dose (pERK) | 1.235 fold change | Standard Deviation 0.295 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, Pre-dose (Tot ERK) | 1.223 fold change | Standard Deviation 0.476 |
| MSC1936369B Regimen 1 | 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) | C1D8, Pre-dose (Tot ERK) | 1.233 fold change | Standard Deviation 0.674 |
| MSC1936369B Regimen 1 | 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) | C1D5, Pre-dose (pERK) | 2.722 fold change | Standard Deviation 1.326 |
| MSC1936369B Regimen 1 | 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) | C1D8, Pre-dose (pERK) | 4.48 fold change | Standard Deviation 2.119 |
| MSC1936369B Regimen 1 | 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) | C3D1, 4 h Post-dose (Tot ERK) | 0.674 fold change | Standard Deviation 0.304 |
| MSC1936369B Regimen 1 | 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) | C1D5, Pre-dose (Tot ERK) | 1.163 fold change | Standard Deviation 0.146 |
| MSC1936369B Regimen 1 | 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) | C1D2, Pre-dose (Tot ERK) | 1.075 fold change | Standard Deviation 0.103 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, Pre-dose (pERK) | 3.257 fold change | Standard Deviation 1.671 |
| MSC1936369B Regimen 1 | 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) | C3D1, Pre-dose (Tot ERK) | 1.074 fold change | Standard Deviation 0.34 |
| MSC1936369B Regimen 1 | 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) | C1D1, 8 h post-dose (Tot ERK) | 1.058 fold change | Standard Deviation 0.16 |
| MSC1936369B Regimen 1 | 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) | C1D1, 4 h post-dose (Tot ERK) | 1.059 fold change | Standard Deviation 0.621 |
| MSC1936369B Regimen 1 | 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) | C1D12-15, 2 h Post-dose (pERK) | 1.252 fold change | Standard Deviation 0.217 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 8 h post-dose (pERK) | 1.454 fold change | Standard Deviation 0.403 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, Pre-dose (pERK) | 3.937 fold change | Standard Deviation 1.662 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 2 h post-dose (pERK) | 1.305 fold change | Standard Deviation 0.755 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 4 h post-dose (pERK) | 3.422 fold change | Standard Deviation 1.902 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D2, Pre-dose (pERK) | 2.411 fold change | Standard Deviation 1.031 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D8, Pre-dose (pERK) | 2.868 fold change | Standard Deviation 1.473 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, Pre-dose (pERK) | 3.265 fold change | Standard Deviation 1.845 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 2 h Post-dose (pERK) | 1.293 fold change | Standard Deviation 0.447 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 8 h Post-dose (pERK) | 1.653 fold change | Standard Deviation 0.571 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 24 h Post-dose (pERK) | 2.476 fold change | Standard Deviation 0.958 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, Pre-dose (pERK) | 3.716 fold change | Standard Deviation 1.875 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, 2 h Post-dose (pERK) | 1.288 fold change | Standard Deviation 0.327 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, 4 h Post-dose (pERK) | 2.688 fold change | Standard Deviation 2.065 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, Pre-dose (Tot ERK) | 1.075 fold change | Standard Deviation 0.25 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 2 h post-dose (Tot ERK) | 1.069 fold change | Standard Deviation 0.247 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 4 h post-dose (Tot ERK) | 1.012 fold change | Standard Deviation 0.286 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D1, 8 h post-dose (Tot ERK) | 1.095 fold change | Standard Deviation 0.31 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D2, Pre-dose (Tot ERK) | 1.13 fold change | Standard Deviation 0.455 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D8, Pre-dose (Tot ERK) | 1.108 fold change | Standard Deviation 0.353 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, Pre-dose (Tot ERK) | 1.118 fold change | Standard Deviation 0.268 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 2 h Post-dose (Tot ERK) | 1.125 fold change | Standard Deviation 0.34 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 8 h Post-dose (Tot ERK) | 1.041 fold change | Standard Deviation 0.237 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C1D12-15, 24 h Post-dose (Tot ERK) | 1.045 fold change | Standard Deviation 0.183 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, Pre-dose (Tot ERK) | 1.138 fold change | Standard Deviation 0.306 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, 2 h Post-dose (Tot ERK) | 1.251 fold change | Standard Deviation 0.29 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | 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) | C3D1, 4 h Post-dose (Tot ERK) | 1.052 fold change | Standard Deviation 0.182 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, Pre-dose (pERK) | 3.241 fold change | Standard Deviation 2.249 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, 2 h post-dose (pERK) | 1.178 fold change | Standard Deviation 0.194 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 24 h Post-dose (Tot ERK) | 1.048 fold change | Standard Deviation 0.139 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 24 h Post-dose (pERK) | 2.598 fold change | Standard Deviation 1.185 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 2 h Post-dose (Tot ERK) | 1.335 fold change | Standard Deviation 0.754 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D8, Pre-dose (Tot ERK) | 0.944 fold change | Standard Deviation 0.117 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D2, Pre-dose (Tot ERK) | 1.013 fold change | Standard Deviation 0.273 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 8 h Post-dose (pERK) | 1.902 fold change | Standard Deviation 0.87 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, 8 h post-dose (pERK) | 1.878 fold change | Standard Deviation 0.836 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D2, Pre-dose (pERK) | 3.081 fold change | Standard Deviation 1.249 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, Pre-dose (pERK) | 4.121 fold change | Standard Deviation 1.743 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, Pre-dose (Tot ERK) | 1.02 fold change | Standard Deviation 0.169 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, 8 h post-dose (Tot ERK) | 1.078 fold change | Standard Deviation 0.143 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 2 h Post-dose (pERK) | 1.471 fold change | Standard Deviation 0.529 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, 8 h Post-dose (Tot ERK) | 1.044 fold change | Standard Deviation 0.238 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D1, 2 h post-dose (Tot ERK) | 1.078 fold change | Standard Deviation 0.151 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D12-15, Pre-dose (Tot ERK) | 1.333 fold change | Standard Deviation 0.878 |
| MSC1936369B Regimen 3 Once Daily (QD) | 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) | C1D8, Pre-dose (pERK) | 2.541 fold change | Standard Deviation 1.338 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, Pre-dose (pERK) | 2.16 fold change | Standard Deviation 0.814 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, 2 h post-dose (pERK) | 1.249 fold change | Standard Deviation 0.219 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, 8 h post-dose (Tot ERK) | 1.098 fold change | Standard Deviation 0.161 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D8, Pre-dose (pERK) | 2.235 fold change | Standard Deviation 0.739 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, Pre-dose (pERK) | 3.629 fold change | Standard Deviation 1.491 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D2, Pre-dose (Tot ERK) | 1.108 fold change | Standard Deviation 0.154 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D2, Pre-dose (pERK) | 2.069 fold change | Standard Deviation 0.748 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D8, Pre-dose (Tot ERK) | 1.049 fold change | Standard Deviation 0.133 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 24 h Post-dose (Tot ERK) | 1.068 fold change | Standard Deviation 0.141 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, Pre-dose (Tot ERK) | 1.047 fold change | Standard Deviation 0.144 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, 8 h post-dose (pERK) | 1.821 fold change | Standard Deviation 0.514 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 24 h Post-dose (pERK) | 2.043 fold change | Standard Deviation 0.76 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 8 h Post-dose (pERK) | 1.98 fold change | Standard Deviation 0.827 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 2 h Post-dose (Tot ERK) | 1.059 fold change | Standard Deviation 0.14 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 2 h Post-dose (pERK) | 1.315 fold change | Standard Deviation 0.218 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, Pre-dose (Tot ERK) | 1.086 fold change | Standard Deviation 0.277 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D1, 2 h post-dose (Tot ERK) | 1.079 fold change | Standard Deviation 0.193 |
| MSC1936369B Regimen 3 Twice Daily | 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) | C1D12-15, 8 h Post-dose (Tot ERK) | 1.026 fold change | Standard Deviation 0.146 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.633 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.52 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 0.533 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 0.500 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 0.750 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.52 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.000 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.000 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.000 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.517 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.500 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.017 Hours (h) |
| MSC1936369B 14 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.500 Hours (h) |
| MSC1936369B 14 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.000 Hours (h) |
| MSC1936369B 14 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.500 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.500 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.000 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.000 Hours (h) |
| MSC1936369B 45 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.017 Hours (h) |
| MSC1936369B 45 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 2.000 Hours (h) |
| MSC1936369B 45 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.508 Hours (h) |
| MSC1936369B 68 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.000 Hours (h) |
| MSC1936369B 68 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.000 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.500 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.483 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 1.767 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C3D1 | 2.000 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D1 | 1.017 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 1 | C1D12 | 1.083 Hours (h) |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: The food effect analysis set (FES). Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 1.600 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 2.033 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 1.000 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 6.000 Hours (h) |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.250 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.500 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.017 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.000 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 0.967 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2.000 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.258 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.000 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.000 Hours (h) |
| MSC1936369B Regimen 3 Twice Daily | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 0.667 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.500 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 0.533 Hours (h) |
| MSC1936369B 7 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.008 Hours (h) |
| MSC1936369B 14 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.500 Hours (h) |
| MSC1936369B 14 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.500 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.017 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.000 Hours (h) |
| MSC1936369B 28 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.50 Hours (h) |
| MSC1936369B 45 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 0.500 Hours (h) |
| MSC1936369B 45 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.500 Hours (h) |
| MSC1936369B 68 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.000 Hours (h) |
| MSC1936369B 68 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.250 Hours (h) |
| MSC1936369B 68 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 0.500 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.500 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.500 Hours (h) |
| MSC1936369B 94 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 2.000 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.042 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 2.000 Hours (h) |
| MSC1936369B 120 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.250 Hours (h) |
| MSC1936369B 150 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.500 Hours (h) |
| MSC1936369B 150 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.333 Hours (h) |
| MSC1936369B 150 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.517 Hours (h) |
| MSC1936369B 195 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 1.250 Hours (h) |
| MSC1936369B 195 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.250 Hours (h) |
| MSC1936369B 195 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.000 Hours (h) |
| MSC1936369B 255 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 1.458 Hours (h) |
| MSC1936369B 255 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 2.000 Hours (h) |
| MSC1936369B 255 mg | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 1.000 Hours (h) |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 1.033 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 2.500 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 2.000 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 1.492 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 1.000 Hours (h) |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 1.467 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 1.500 Hours (h) |
| MSC1936369B Regimen 1 | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 1.500 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 1.500 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 1.183 Hours (h) |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 1.000 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 0.667 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 1.467 Hours (h) |
| MSC1936369B Regimen 3 Once Daily (QD) | Time to Reach Maximum Plasma Concentration (Tmax) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 1.500 Hours (h) |
Secondary
Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0-inf. 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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 70.60 Liter per hour | Geometric Coefficient of Variation 77.3 |
| MSC1936369B Regimen 3 Twice Daily | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 132.69 Liter per hour | — |
| MSC1936369B 7 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 44.55 Liter per hour | — |
| MSC1936369B 7 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 114.26 Liter per hour | Geometric Coefficient of Variation 66.9 |
| MSC1936369B 7 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C3D1 | 217.56 Liter per hour | — |
| MSC1936369B 14 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 62.53 Liter per hour | Geometric Coefficient of Variation 92.6 |
| MSC1936369B 14 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 59.80 Liter per hour | Geometric Coefficient of Variation 70.2 |
| MSC1936369B 14 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C3D1 | 104.07 Liter per hour | — |
| MSC1936369B 28 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 37.49 Liter per hour | Geometric Coefficient of Variation 55.2 |
| MSC1936369B 28 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 48.76 Liter per hour | Geometric Coefficient of Variation 50 |
| MSC1936369B 45 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 48.69 Liter per hour | Geometric Coefficient of Variation 32.7 |
| MSC1936369B 45 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C3D1 | 82.35 Liter per hour | — |
| MSC1936369B 45 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 49.37 Liter per hour | Geometric Coefficient of Variation 43.8 |
| MSC1936369B 68 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 35.80 Liter per hour | Geometric Coefficient of Variation 99.7 |
| MSC1936369B 68 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 40.01 Liter per hour | Geometric Coefficient of Variation 36.1 |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 50.45 Liter per hour | Geometric Coefficient of Variation 41.2 |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 50.88 Liter per hour | Geometric Coefficient of Variation 19.6 |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C3D1 | 107.06 Liter per hour | — |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D12 | 61.44 Liter per hour | Geometric Coefficient of Variation 42.3 |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C1D1 | 47.82 Liter per hour | Geometric Coefficient of Variation 53.3 |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 1 | C3D1 | 72.25 Liter per hour | Geometric Coefficient of Variation 35.7 |
Secondary
Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect)
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
Population: The food effect analysis set (FES). Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 56.94 Liter per hour | Geometric Coefficient of Variation 48.7 |
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 60.17 Liter per hour | Geometric Coefficient of Variation 41.8 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect) | Fasted | 44.85 Liter per hour | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (With Food Effect) | Fed | 26.62 Liter per hour | — |
Secondary
Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect)
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 3 Twice Daily | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 89.34 Liter per hour | — |
| MSC1936369B Regimen 3 Twice Daily | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 59.55 Liter per hour | — |
| MSC1936369B 7 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 134.9 Liter per hour | — |
| MSC1936369B 7 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 90.76 Liter per hour | Geometric Coefficient of Variation 18.3 |
| MSC1936369B 14 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 86.72 Liter per hour | Geometric Coefficient of Variation 12.5 |
| MSC1936369B 14 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 64.09 Liter per hour | Geometric Coefficient of Variation 62.1 |
| MSC1936369B 28 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 43.28 Liter per hour | Geometric Coefficient of Variation 20.7 |
| MSC1936369B 28 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 45.10 Liter per hour | Geometric Coefficient of Variation 12.7 |
| MSC1936369B 45 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 49.65 Liter per hour | Geometric Coefficient of Variation 15.4 |
| MSC1936369B 45 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 54.85 Liter per hour | Geometric Coefficient of Variation 15.7 |
| MSC1936369B 68 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 41.08 Liter per hour | Geometric Coefficient of Variation 19.1 |
| MSC1936369B 68 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 76.77 Liter per hour | Geometric Coefficient of Variation 111 |
| MSC1936369B 68 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 43.76 Liter per hour | Geometric Coefficient of Variation 122.4 |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 51.47 Liter per hour | Geometric Coefficient of Variation 17.9 |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 59.31 Liter per hour | — |
| MSC1936369B 94 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 61.61 Liter per hour | Geometric Coefficient of Variation 13.2 |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 48.76 Liter per hour | Geometric Coefficient of Variation 64.3 |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 49.50 Liter per hour | Geometric Coefficient of Variation 109.7 |
| MSC1936369B 120 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 92.42 Liter per hour | Geometric Coefficient of Variation 84.1 |
| MSC1936369B 150 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 81.22 Liter per hour | Geometric Coefficient of Variation 65.4 |
| MSC1936369B 150 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 65.57 Liter per hour | Geometric Coefficient of Variation 77.4 |
| MSC1936369B 150 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 61.04 Liter per hour | Geometric Coefficient of Variation 53 |
| MSC1936369B 195 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 53.49 Liter per hour | Geometric Coefficient of Variation 64.3 |
| MSC1936369B 195 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 54.13 Liter per hour | Geometric Coefficient of Variation 46.2 |
| MSC1936369B 195 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 72.33 Liter per hour | Geometric Coefficient of Variation 63.8 |
| MSC1936369B 255 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C3D1 | 44.23 Liter per hour | Geometric Coefficient of Variation 37.5 |
| MSC1936369B 255 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D15 | 42.20 Liter per hour | Geometric Coefficient of Variation 5.9 |
| MSC1936369B 255 mg | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 2 (Without Food Effect) | C1D1 | 60.63 Liter per hour | Geometric Coefficient of Variation 53.4 |
Secondary
Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily
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
Population: PKS analysis set. Here Number Analyzed signifies those who were evaluated at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 47.88 Liter per hour | Geometric Coefficient of Variation 96.9 |
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 48.31 Liter per hour | Geometric Coefficient of Variation 103.9 |
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 53.36 Liter per hour | — |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C1D1 | 56.91 Liter per hour | Geometric Coefficient of Variation 56.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C1D15 | 62.85 Liter per hour | Geometric Coefficient of Variation 63.6 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Once Daily | C3D1 | 75.63 Liter per hour | Geometric Coefficient of Variation 59.6 |
Secondary
Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 126.1 Liter per hour | — |
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 114.82 Liter per hour | — |
| MSC1936369B Regimen 1 | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 71.44 Liter per hour | Geometric Coefficient of Variation 69.3 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 103.3 Liter per hour | Geometric Coefficient of Variation 66.9 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 66.89 Liter per hour | Geometric Coefficient of Variation 52.1 |
| MSC1936369B Regimen 2 (Without Food Effect + With Food Effect) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 80.83 Liter per hour | Geometric Coefficient of Variation 47.1 |
| MSC1936369B Regimen 3 Once Daily (QD) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C3D1 | 77.09 Liter per hour | Geometric Coefficient of Variation 21 |
| MSC1936369B Regimen 3 Once Daily (QD) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D15 | 94.48 Liter per hour | Geometric Coefficient of Variation 71.2 |
| MSC1936369B Regimen 3 Once Daily (QD) | Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of MSC1936369B: Regimen 3 Twice Daily | C1D1 | 83.86 Liter per hour | Geometric Coefficient of Variation 67.2 |