Trial Outcomes & Findings for Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies (NCT NCT01117623)
NCT ID: NCT01117623
Last Updated: 2015-11-18
Results Overview
The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
86 participants
Primary outcome timeframe
Within first 4 weeks of treatment
Results posted on
2015-11-18
Participant Flow
Adult participants with advanced, histologically or cytologically confirmed solid tumors (including non-small-cell lung cancer (NSCLC) participants enrolled in the expansion portion of the study), malignant lymphomas, or multiple myeloma were enrolled in 5 centers in the USA from 01 FEB 2007 to 22 Apr 2011.
109 (73 male and 36 female) participants were screened according to the inclusion and exclusion criteria to determine their appropriateness for inclusion in the study, and 86 (54 male and 32 female) participants were included at 5 centers, valid for safety population, 81 participants valid for ITT efficacy analysis and PK population.
Participant milestones
| Measure |
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
Participants in the dose-escalation cohort received a single 20 mg oral co-precipitate (CP) tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
8
|
11
|
6
|
10
|
16
|
6
|
26
|
|
Overall Study
ITT Efficacy Analysis Population
|
3
|
8
|
11
|
5
|
10
|
16
|
6
|
22
|
|
Overall Study
PK Population
|
3
|
8
|
10
|
6
|
10
|
14
|
6
|
24
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
8
|
11
|
6
|
10
|
16
|
6
|
26
|
Reasons for withdrawal
| Measure |
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
Participants in the dose-escalation cohort received a single 20 mg oral co-precipitate (CP) tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
4
|
0
|
2
|
0
|
0
|
2
|
|
Overall Study
Disease progression, recurrence, relapse
|
3
|
6
|
5
|
6
|
8
|
14
|
5
|
22
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
0
|
1
|
1
|
1
|
|
Overall Study
Non-compliance with study medication
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Invest. text: completed all planned txs
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Baseline characteristics by cohort
| Measure |
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=11 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=16 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=6 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=26 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
63.3 Years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
55.3 Years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
61.9 Years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
59.2 Years
STANDARD_DEVIATION 10.7 • n=4 Participants
|
55.7 Years
STANDARD_DEVIATION 13.7 • n=21 Participants
|
56.6 Years
STANDARD_DEVIATION 13.2 • n=10 Participants
|
56.7 Years
STANDARD_DEVIATION 13.1 • n=115 Participants
|
62.4 Years
STANDARD_DEVIATION 12.2 • n=6 Participants
|
59.6 Years
STANDARD_DEVIATION 11.8 • n=6 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
9 Participants
n=6 Participants
|
32 Participants
n=6 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
12 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
17 Participants
n=6 Participants
|
54 Participants
n=6 Participants
|
PRIMARY outcome
Timeframe: Within first 4 weeks of treatmentPopulation: Safety Population; dose escalation cohorts only
The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=37 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
100 mg
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Cmax in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC
Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
Regorafenib (n=3,7,10,6,10,14,4,24)
|
0.330 mg/L
Geometric Coefficient of Variation 14.8
|
0.422 mg/L
Geometric Coefficient of Variation 27.4
|
1.25 mg/L
Geometric Coefficient of Variation 30.7
|
1.87 mg/L
Geometric Coefficient of Variation 24.0
|
1.90 mg/L
Geometric Coefficient of Variation 51.2
|
1.38 mg/L
Geometric Coefficient of Variation 98
|
1.42 mg/L
Geometric Coefficient of Variation 76
|
1.25 mg/L
Geometric Coefficient of Variation 68.5
|
|
Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
|
0.0181 mg/L
Geometric Coefficient of Variation 244
|
0.0867 mg/L
Geometric Coefficient of Variation 110
|
0.401 mg/L
Geometric Coefficient of Variation 51.2
|
0.645 mg/L
Geometric Coefficient of Variation 43.2
|
0.606 mg/L
Geometric Coefficient of Variation 97.2
|
0.42 mg/L
Geometric Coefficient of Variation 154
|
0.54 mg/L
Geometric Coefficient of Variation 129
|
0.388 mg/L
Geometric Coefficient of Variation 190
|
|
Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
|
0.00290 mg/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.00738 mg/L
Geometric Coefficient of Variation 124
|
0.0299 mg/L
Geometric Coefficient of Variation 118
|
0.0459 mg/L
Geometric Coefficient of Variation 59.2
|
0.0500 mg/L
Geometric Coefficient of Variation 140
|
0.036 mg/L
Geometric Coefficient of Variation 110
|
0.035 mg/L
Geometric Coefficient of Variation 352
|
0.321 mg/L
Geometric Coefficient of Variation 142
|
PRIMARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dosePopulation: PK population; Number of Participants with at least one evaluable AUC were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10 (M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
Regorafenib (n=3,5,5,6,6,9,3,19)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
16.3 mg*h/L
Geometric Coefficient of Variation 76.3
|
43.7 mg*h/L
Geometric Coefficient of Variation 34.9
|
52.9 mg*h/L
Geometric Coefficient of Variation 64.6
|
52.5 mg*h/L
Geometric Coefficient of Variation 66.4
|
45.2 mg*h/L
Geometric Coefficient of Variation 84.3
|
57.7 mg*h/L
Geometric Coefficient of Variation 30.9
|
33.5 mg*h/L
Geometric Coefficient of Variation 43.9
|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
3.53 mg*h/L
Geometric Coefficient of Variation 161
|
12.8 mg*h/L
Geometric Coefficient of Variation 37.0
|
21.0 mg*h/L
Geometric Coefficient of Variation 71.5
|
19.5 mg*h/L
Geometric Coefficient of Variation 20.3
|
15.3 mg*h/L
Geometric Coefficient of Variation 69.9
|
27.2 mg*h/L
Geometric Coefficient of Variation 74.6
|
11.6 mg*h/L
Geometric Coefficient of Variation 77.8
|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
15.8 mg*h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA mg*h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
PRIMARY outcome
Timeframe: Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.Population: Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Cmax at Steady State During a Dosing Interval (Cmax,ss)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
1.27 mg/L
Geometric Coefficient of Variation 19.4
|
1.50 mg/L
Geometric Coefficient of Variation 37.0
|
4.27 mg/L
Geometric Coefficient of Variation 22.9
|
3.62 mg/L
Geometric Coefficient of Variation 5.77
|
5.37 mg/L
Geometric Coefficient of Variation 30.9
|
NA mg/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
2.69 mg/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
2.55 mg/L
Geometric Coefficient of Variation 92.4
|
|
Cmax at Steady State During a Dosing Interval (Cmax,ss)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
0.0912 mg/L
Geometric Coefficient of Variation 39.5
|
0.520 mg/L
Geometric Coefficient of Variation 74.3
|
2.48 mg/L
Geometric Coefficient of Variation 36.3
|
2.97 mg/L
Geometric Coefficient of Variation 217
|
2.20 mg/L
Geometric Coefficient of Variation 106
|
NA mg/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
2.40 mg/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.911 mg/L
Geometric Coefficient of Variation 126
|
|
Cmax at Steady State During a Dosing Interval (Cmax,ss)
M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5)
|
0.00911 mg/L
Geometric Coefficient of Variation 15.7
|
0.174 mg/L
Geometric Coefficient of Variation 151
|
1.38 mg/L
Geometric Coefficient of Variation 87.0
|
3.29 mg/L
Geometric Coefficient of Variation 1400
|
0.948 mg/L
Geometric Coefficient of Variation 343
|
NA mg/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
1.59 mg/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.349 mg/L
Geometric Coefficient of Variation 153
|
PRIMARY outcome
Timeframe: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.Population: Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24),ss in at least one analyte in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
12.9 mg*h/mL
Geometric Coefficient of Variation 21.2
|
18.1 mg*h/mL
Geometric Coefficient of Variation 35.9
|
49.6 mg*h/mL
Geometric Coefficient of Variation 18.5
|
40.6 mg*h/mL
Geometric Coefficient of Variation 32.9
|
60.4 mg*h/mL
Geometric Coefficient of Variation 18.5
|
NA mg*h/mL
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
39.2 mg*h/mL
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
35.8 mg*h/mL
Geometric Coefficient of Variation 83.9
|
|
AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
1.11 mg*h/mL
Geometric Coefficient of Variation 42.9
|
7.20 mg*h/mL
Geometric Coefficient of Variation 56.7
|
31.5 mg*h/mL
Geometric Coefficient of Variation 25.2
|
40.9 mg*h/mL
Geometric Coefficient of Variation 245
|
29.7 mg*h/mL
Geometric Coefficient of Variation 88.8
|
NA mg*h/mL
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
46.8 mg*h/mL
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
14.6 mg*h/mL
Geometric Coefficient of Variation 104
|
|
AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)
M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5)
|
0.122 mg*h/mL
Geometric Coefficient of Variation 18.7
|
2.22 mg*h/mL
Geometric Coefficient of Variation 136
|
18.6 mg*h/mL
Geometric Coefficient of Variation 58.1
|
44.4 mg*h/mL
Geometric Coefficient of Variation 3050
|
12.9 mg*h/mL
Geometric Coefficient of Variation 231
|
NA mg*h/mL
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
34.3 mg*h/mL
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
6.17 mg*h/mL
Geometric Coefficient of Variation 133
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable AUC(0-tlast) in at least one analyte were 1(M-5) in 20mg; 7 (regorafenib and M-2) and 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M5) in NSCLC
The AUC(0-tlast) is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
Regorafenib (n=3,7,10,6,10,14,4,24)
|
7.98 mg*h/L
Geometric Coefficient of Variation 28.0
|
9.12 mg*h/L
Geometric Coefficient of Variation 38.8
|
32.7 mg*h/L
Geometric Coefficient of Variation 37.9
|
33.5 mg*h/L
Geometric Coefficient of Variation 60.4
|
35.8 mg*h/L
Geometric Coefficient of Variation 57.0
|
26.8 mg*h/L
Geometric Coefficient of Variation 67.5
|
33.0 mg*h/L
Geometric Coefficient of Variation 112
|
18.7 mg*h/L
Geometric Coefficient of Variation 55.3
|
|
AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
|
0.384 mg*h/L
Geometric Coefficient of Variation 330
|
2.02 mg*h/L
Geometric Coefficient of Variation 108
|
11.3 mg*h/L
Geometric Coefficient of Variation 47.4
|
14.2 mg*h/L
Geometric Coefficient of Variation 53.4
|
13.6 mg*h/L
Geometric Coefficient of Variation 82.6
|
8.84 mg*h/L
Geometric Coefficient of Variation 122
|
13.4 mg*h/L
Geometric Coefficient of Variation 194
|
6.54 mg*h/L
Geometric Coefficient of Variation 156
|
|
AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
|
0.0275 mg*h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.165 mg*h/L
Geometric Coefficient of Variation 254
|
0.976 mg*h/L
Geometric Coefficient of Variation 111
|
1.51 mg*h/L
Geometric Coefficient of Variation 71.1
|
1.54 mg*h/L
Geometric Coefficient of Variation 71.1
|
1.02 mg*h/L
Geometric Coefficient of Variation 122
|
0.821 mg*h/L
Geometric Coefficient of Variation 587
|
0.821 mg*h/L
Geometric Coefficient of Variation 254
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dosePopulation: PK population; Number of Participants with at least one evaluable AUC/D were 5 (regorafenib) and 6 (M-2) in 40mg; 5 (regorafenib and M-2) in 100 mg; 3 (M-2) in 120 mg; 6 (regorafenib and M-2) in 140 mg; 9 (regorafenib), 10 (M-2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M-2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M-2) in NSCLC
The AUC/D is a measure of systemic drug exposure (AUC) after the first single dose, which is then divided by that dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
Regorafenib (n=3,5,5,6,6,9,3,19)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
0.407 h/L
Geometric Coefficient of Variation 76.3
|
0.437 h/L
Geometric Coefficient of Variation 34.9
|
0.441 h/L
Geometric Coefficient of Variation 64.6
|
0.375 h/L
Geometric Coefficient of Variation 66.4
|
0.452 h/L
Geometric Coefficient of Variation 84.3
|
0.577 h/L
Geometric Coefficient of Variation 30.9
|
0.355 h/L
Geometric Coefficient of Variation 43.9
|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
0.0855 h/L
Geometric Coefficient of Variation 161
|
0.124 h/L
Geometric Coefficient of Variation 37.0
|
0.169 h/L
Geometric Coefficient of Variation 71.5
|
0.135 h/L
Geometric Coefficient of Variation 20.3
|
0.148 h/L
Geometric Coefficient of Variation 69.9
|
0.263 h/L
Geometric Coefficient of Variation 74.6
|
0.113 h/L
Geometric Coefficient of Variation 77.8
|
|
Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
0.0157 h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h/L
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Cmax/D in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC
Cmax/D refers to the highest measured drug concentration after a single dose administration, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
Regorafenib (n=3,7,10,6,10,14,4,24)
|
0.0165 1/L
Geometric Coefficient of Variation 14.8
|
0.0106 1/L
Geometric Coefficient of Variation 27.4
|
0.0125 1/L
Geometric Coefficient of Variation 30.7
|
0.0156 1/L
Geometric Coefficient of Variation 24.0
|
0.0136 1/L
Geometric Coefficient of Variation 51.2
|
0.0138 1/L
Geometric Coefficient of Variation 97.9
|
0.0142 1/L
Geometric Coefficient of Variation 76.1
|
0.0125 1/L
Geometric Coefficient of Variation 68.5
|
|
Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24)
|
0.000874 1/L
Geometric Coefficient of Variation 244
|
0.00210 1/L
Geometric Coefficient of Variation 110
|
0.00388 1/L
Geometric Coefficient of Variation 51.2
|
0.00520 1/L
Geometric Coefficient of Variation 43.2
|
0.00419 1/L
Geometric Coefficient of Variation 97.2
|
0.00404 1/L
Geometric Coefficient of Variation 154
|
0.00526 1/L
Geometric Coefficient of Variation 129
|
0.00376 1/L
Geometric Coefficient of Variation 190
|
|
Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
|
0.000114 1/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.000184 1/L
Geometric Coefficient of Variation 124
|
0.000298 1/L
Geometric Coefficient of Variation 118
|
0.000381 1/L
Geometric Coefficient of Variation 59.2
|
0.000355 1/L
Geometric Coefficient of Variation 140
|
0.000355 1/L
Geometric Coefficient of Variation 110
|
0.000351 1/L
Geometric Coefficient of Variation 352
|
0.000320 1/L
Geometric Coefficient of Variation 142
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.Population: Pharmacokinetic population; Number of Participants with an evaluable Tmax in at least one analyte were 1 (M-5) in 20 mg; 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M-5) in NSCLC
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Regorafenib (n=3,8,10,6,10,14,4,24)
|
8.00 h
Interval 4.0 to 34.0
|
2.02 h
Interval 2.0 to 10.0
|
5.00 h
Interval 2.0 to 48.0
|
6.00 h
Interval 2.0 to 24.0
|
3.01 h
Interval 1.0 to 24.7
|
3.03 h
Interval 2.0 to 24.0
|
3.00 h
Interval 2.0 to 10.0
|
2.00 h
Interval 1.0 to 48.1
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
M2 (BAY75-7495) (n=3,8,10,6,10,14,4,24)
|
8.00 h
Interval 4.0 to 24.6
|
2.02 h
Interval 2.0 to 10.0
|
10.0 h
Interval 2.0 to 48.0
|
9.00 h
Interval 2.0 to 24.0
|
4.00 h
Interval 2.0 to 24.7
|
3.01 h
Interval 2.0 to 24.0
|
10.0 h
Interval 8.0 to 24.1
|
2.01 h
Interval 2.0 to 48.0
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22)
|
48.0 h
Interval 48.0 to 48.0
|
47.8 h
Interval 10.0 to 48.0
|
48.0 h
Interval 24.0 to 48.0
|
24.6 h
Interval 10.0 to 48.0
|
47.6 h
Interval 24.1 to 48.0
|
46.8 h
Interval 4.0 to 48.6
|
34.9 h
Interval 24.0 to 46.8
|
47.8 h
Interval 4.0 to 48.4
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.Population: PK population; Number of Patients with at least an evaluable T1/2 were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (regorafenib and M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10(M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC
T1/2 is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Half-life Associated With the Terminal Slope (T1/2)
Regorafenib (n=3,5,5,3,6,9,22,19)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
41.6 h
Geometric Coefficient of Variation 41.1
|
31.6 h
Geometric Coefficient of Variation 32.5
|
27.7 h
Geometric Coefficient of Variation 47.8
|
23.2 h
Geometric Coefficient of Variation 43.6
|
25.2 h
Geometric Coefficient of Variation 52.0
|
745.3 h
Geometric Coefficient of Variation 79.7
|
33.3 h
Geometric Coefficient of Variation 64.8
|
|
Half-life Associated With the Terminal Slope (T1/2)
M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
40.3 h
Geometric Coefficient of Variation 52.3
|
24.8 h
Geometric Coefficient of Variation 28.6
|
22.9 h
Geometric Coefficient of Variation 27.6
|
22.7 h
Geometric Coefficient of Variation 64.7
|
24.0 h
Geometric Coefficient of Variation 56.3
|
19.2 h
Geometric Coefficient of Variation 16.4
|
26.4 h
Geometric Coefficient of Variation 73.4
|
|
Half-life Associated With the Terminal Slope (T1/2)
M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
68.7 h
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
NA h
Geometric Coefficient of Variation NA
not calculated due to no evaluable data (i.e. insufficient plasma concentrations)
|
SECONDARY outcome
Timeframe: Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Cmax,ss/D refers to the highest measured drug concentration after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
0.0636 1/L
Geometric Coefficient of Variation 19.4
|
0.0374 1/L
Geometric Coefficient of Variation 37.0
|
0.0427 1/L
Geometric Coefficient of Variation 22.9
|
0.0302 1/L
Geometric Coefficient of Variation 5.77
|
0.0383 1/L
Geometric Coefficient of Variation 30.9
|
NA 1/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.0269 1/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.0255 1/L
Geometric Coefficient of Variation 92.4
|
|
Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
0.00441 1/L
Geometric Coefficient of Variation 39.5
|
0.0126 1/L
Geometric Coefficient of Variation 74.3
|
0.0241 1/L
Geometric Coefficient of Variation 36.3
|
0.0240 1/L
Geometric Coefficient of Variation 217
|
0.0152 1/L
Geometric Coefficient of Variation 106
|
NA 1/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.0232 1/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.00881 1/L
Geometric Coefficient of Variation 126
|
|
Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D)
M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5)
|
0.000454 1/L
Geometric Coefficient of Variation 15.7
|
0.00434 1/L
Geometric Coefficient of Variation 151
|
0.0137 1/L
Geometric Coefficient of Variation 87.9
|
0.0273 1/L
Geometric Coefficient of Variation 1400
|
0.00674 1/L
Geometric Coefficient of Variation 343
|
NA 1/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.0159 1/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.00347 1/L
Geometric Coefficient of Variation 153
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24)ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
AUC(0-24)ss/D is a measure of systemic drug exposure (AUC) over 24 hours after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
0.644 h/L
Geometric Coefficient of Variation 21.2
|
0.452 h/L
Geometric Coefficient of Variation 35.9
|
0.496 h/L
Geometric Coefficient of Variation 18.5
|
0.338 h/L
Geometric Coefficient of Variation 32.9
|
0.431 h/L
Geometric Coefficient of Variation 18.5
|
NA h/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.392 h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.358 h/L
Geometric Coefficient of Variation 83.8
|
|
AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
0.0538 h/L
Geometric Coefficient of Variation 42.9
|
0.174 h/L
Geometric Coefficient of Variation 56.7
|
0.305 h/L
Geometric Coefficient of Variation 25.2
|
0.330 h/L
Geometric Coefficient of Variation 245
|
0.205 h/L
Geometric Coefficient of Variation 88.8
|
NA h/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.453 h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.141 h/L
Geometric Coefficient of Variation 104
|
|
AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D)
M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5)
|
0.00609 h/L
Geometric Coefficient of Variation 18.7
|
0.0552 h/L
Geometric Coefficient of Variation 136
|
0.185 h/L
Geometric Coefficient of Variation 58.1
|
0.368 h/L
Geometric Coefficient of Variation 3050
|
0.0916 h/L
Geometric Coefficient of Variation 231
|
NA h/L
Geometric Coefficient of Variation NA
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.342 h/L
Geometric Coefficient of Variation NA
we have one data point only, n=1, calculation not possible
|
0.0615 h/L
Geometric Coefficient of Variation 133
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Tmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
Tmax,ss refers to the time after multiple dose administration and after a steady state concentration has been reached when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
2.00 h
Interval 2.0 to 4.0
|
2.00 h
Interval 1.0 to 10.0
|
1.25 h
Interval 0.0 to 4.0
|
2.00 h
Interval 2.0 to 2.0
|
2.00 h
Interval 1.0 to 4.0
|
NA h
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
4.03 h
Interval 4.03 to 4.03
|
4.00 h
Interval 2.0 to 10.0
|
|
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
2.00 h
Interval 2.0 to 4.0
|
1.50 h
Interval 1.0 to 10.0
|
2.00 h
Interval 0.0 to 8.0
|
2.00 h
Interval 2.0 to 2.0
|
2.00 h
Interval 1.0 to 8.0
|
NA h
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
10.0 h
Interval 10.0 to 10.0
|
4.00 h
Interval 2.0 to 10.0
|
|
Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5)
|
2.00 h
Interval 0.5 to 4.0
|
1.00 h
Interval 1.0 to 1.0
|
1.00 h
Interval 0.0 to 24.0
|
1.50 h
Interval 1.0 to 2.0
|
1.00 h
Interval 0.0 to 8.0
|
NA h
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.00 h
Interval 0.0 to 0.0
|
4.00 h
Interval 0.0 to 10.0
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss and Cmax in at least one analyte were 1 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
RACmax is the ratio of the highest drug concentration at steady state to the highest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Ratio of Cmax,ss/Cmax (RACmax)
Regorafenib (n=3,5,6,2,3,0,1,5)
|
3.78 Ratio
|
3.34 Ratio
|
3.50 Ratio
|
1.53 Ratio
|
2.84 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
1.90 Ratio
|
1.82 Ratio
|
|
Ratio of Cmax,ss/Cmax (RACmax)
M2 (BAY75-7495) (n=3,5,6,2,3,0,1,5)
|
4.86 Ratio
|
4.26 Ratio
|
5.39 Ratio
|
3.06 Ratio
|
3.33 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
3.40 Ratio
|
1.83 Ratio
|
|
Ratio of Cmax,ss/Cmax (RACmax)
M5 (BAY81-8752) (n=1,4,6,2,3,0,1,5)
|
3.80 Ratio
|
22.8 Ratio
|
32.5 Ratio
|
39.3 Ratio
|
18.9 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
45.0 Ratio
|
11.9 Ratio
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable Cmin,ss and Cmin in at least one analyte were 0 (M5) in 20mg; 6 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
RACmin is the ratio of the lowest drug concentration at steady state to the lowest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Ratio of Cmin,ss/Cmin (RACmin)
Regorafenib (n=3,6,6,2,3,0,1,5)
|
4.82 Ratio
|
34.9 Ratio
|
26.1 Ratio
|
413 Ratio
|
10.9 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
7.80 Ratio
|
14.1 Ratio
|
|
Ratio of Cmin,ss/Cmin (RACmin)
M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5)
|
4.81 Ratio
|
10.4 Ratio
|
24.2 Ratio
|
12.6 Ratio
|
3.33 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
103 Ratio
|
11.5 Ratio
|
|
Ratio of Cmin,ss/Cmin (RACmin)
M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5)
|
NA Ratio
3 participants were analyzed. Not calculated due to no participant with an evaluable data
|
26.1 Ratio
|
102 Ratio
|
335 Ratio
|
46.2 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
257 Ratio
|
22.4 Ratio
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: Pharmacokinetic population; Number of Participants with an evaluable AUCt,ss and AUCt in at least one analyte were 0 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC
RAAUC is the ratio of the measure of systemic drug exposure over a specific dosing interval at steady state to the measure of systemic drug exposure over a specific dosing interval after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Ratio of AUCt,ss/AUCt (RAAUC)
M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5)
|
NA Ratio
3 participants were analyzed. Not calculated due to no participant with an evaluable data
|
28.1 Ratio
|
41.2 Ratio
|
34.7 Ratio
|
23.9 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
63.0 Ratio
|
18.5 Ratio
|
|
Ratio of AUCt,ss/AUCt (RAAUC)
Regorafenib (n=3,5,6,2,3,0,1,5)
|
3.20 Ratio
|
3.78 Ratio
|
3.15 Ratio
|
1.37 Ratio
|
3.61 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
2.10 Ratio
|
2.67 Ratio
|
|
Ratio of AUCt,ss/AUCt (RAAUC)
M2 (BAY75-7495) (n=3,5,6,2,3,0,1,5)
|
5.79 Ratio
|
4.72 Ratio
|
4.63 Ratio
|
2.71 Ratio
|
3.60 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
4.60 Ratio
|
2.74 Ratio
|
SECONDARY outcome
Timeframe: Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dosePopulation: PK population; Number of Participants with an evaluable AUCt,ss and AUC in at least one analyte were 0 in 20mg; 3 (regorafenib) and 4 (M2) in 40mg; 3 in 100 mg; 2 (regorafenib) and 0 (M2) in 120 mg; 3 (regorafenib) and 2 (M2) in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 4 in NSCLC; No participants have evaluable data for M5.
RLIN is the ratio of the measure of systemic drug exposure at steady state to the measure of systemic drug exposure after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
n=14 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
n=4 Participants
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
n=24 Participants
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Ratio of AUCt,ss/AUC (RLIN)
M5 (BAY81-8752) (n=0)
|
NA Ratio
3 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
8 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
10 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
6 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
10 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
4 participants were analyzed. Not calculated due to no participant with an evaluable data
|
NA Ratio
24 participants were analyzed. Not calculated due to no participant with an evaluable data
|
|
Ratio of AUCt,ss/AUC (RLIN)
Regorafenib (n=0,3,3,2,3,0,1,4)
|
NA Ratio
3 participants were analyzed. Not calculated due to no participant with an evaluable data
|
1.53 Ratio
|
1.27 Ratio
|
0.600 Ratio
|
2.20 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
0.800 Ratio
|
1.11 Ratio
|
|
Ratio of AUCt,ss/AUC (RLIN)
M2 (BAY75-7495) (n=0,4,3,0,2,0,1,4)
|
NA Ratio
3 participants were analyzed. Not calculated due to no participant with an evaluable data
|
1.63 Ratio
|
2.13 Ratio
|
NA Ratio
6 participants were analyzed. Not calculated due to no participant with an evaluable data
|
1.39 Ratio
|
NA Ratio
14 participants were analyzed. Not calculated due to no participant with an evaluable data
|
2.70 Ratio
|
1.27 Ratio
|
SECONDARY outcome
Timeframe: No data obtainedPopulation: ITT
The analysis of Biomarker VEGF plasma levels is not done
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: No data obtainedPopulation: ITT
The analysis of Biomarker sCEGFR-2 plasma levels is not done.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)Population: Intent-to-treat (ITT) efficacy analysis (set)
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=11 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=5 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Tumor Progression in Dose Escalation Cohort
Participants without progression
|
1 Participants
|
3 Participants
|
9 Participants
|
2 Participants
|
5 Participants
|
—
|
—
|
—
|
|
Tumor Progression in Dose Escalation Cohort
Participants with progression
|
2 Participants
|
5 Participants
|
2 Participants
|
3 Participants
|
5 Participants
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)Population: ITT efficacy analysis (set), expansion cohorts only
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=22 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=22 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Tumor Progression in Expansion Cohort
Participants without progression
|
10 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Progression in Expansion Cohort
Participants with progression
|
12 Participants
|
16 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)Population: ITT efficacy analysis (set)
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=3 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
n=11 Participants
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=5 Participants
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 Participants
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Tumor Response in Dose Escalation Cohort
Not assessable
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Tumor Response in Dose Escalation Cohort
Partial Response (PR)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
|
Tumor Response in Dose Escalation Cohort
Progressive Disease (PD)
|
2 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
—
|
—
|
—
|
|
Tumor Response in Dose Escalation Cohort
Stable Disease (SD)
|
1 Participants
|
2 Participants
|
5 Participants
|
2 Participants
|
4 Participants
|
—
|
—
|
—
|
|
Tumor Response in Dose Escalation Cohort
Progression
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)Population: ITT efficacy analysis (set), expansion cohorts only
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Outcome measures
| Measure |
Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg
n=22 Participants
Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=22 Participants
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
NSCLC Expansion Cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|---|---|---|
|
Tumor Response in Expansion Cohort
Not assessable
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response in Expansion Cohort
Partial Response (PR)
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response in Expansion Cohort
Stable Disease (SD)
|
6 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response in Expansion Cohort
Progressive Disease (PD)
|
10 Participants
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tumor Response in Expansion Cohort
Progression
|
2 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths
Regorafenib (Stivarga, BAY73-4506) 100 mg
Serious events: 31 serious events
Other events: 58 other events
Deaths: 0 deaths
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Serious events: 6 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
n=3 participants at risk
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 participants at risk
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Regorafenib (Stivarga, BAY73-4506) 100 mg
n=59 participants at risk
Participants received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. This arm includes the participants from the dose escalation cohort: Regorafenib 100 mg and the three Expansion Cohorts 'HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg', 'HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg', 'NSCLC Expansion Cohort: Regorafenib 100 mg'.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 participants at risk
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 participants at risk
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Edema: Limb
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Cardiac General - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Conduction abnormality, AV Block - 3rd Degree (Complete AV Block)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Hypertension
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Hypotension
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
SupraVentricular arrhythmia, Sinus tachycardia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Eye disorders
Blurred vision
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Eye disorders
Ocular - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
GI - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Obstruction, GI, Duodenum
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Obstruction, GI, Small bowel NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Constitutional Symptoms - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Death not associated with CTCAE term, Disease Progression NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Fatigue
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Fever
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Abdomen NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Back
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Chest wall
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Chest/thorax NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Joint
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Other (Specify)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Hepatobiliary disorders
Liver dysfunction
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Hepatobiliary disorders
Pancreatitis
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Appendix
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Bladder (urinary)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Blood
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Bronchus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Lung (pneumonia)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Urinary tract NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection with normal ANC, Colon
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy (possibly related to cancer treatment)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neurology - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: motor
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Renal - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
CNS hemorrhage
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
Hemorrhage pulmonary, Respiratory tract NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
Other adverse events
| Measure |
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
n=3 participants at risk
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
n=8 participants at risk
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Regorafenib (Stivarga, BAY73-4506) 100 mg
n=59 participants at risk
Participants received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. This arm includes the participants from the dose escalation cohort: Regorafenib 100 mg and the three Expansion Cohorts 'HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg', 'HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg', 'NSCLC Expansion Cohort: Regorafenib 100 mg'.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
n=6 participants at risk
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
n=10 participants at risk
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
|---|---|---|---|---|---|
|
Infections and infestations
Infection (Documented clinically), Bronchus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Conjunctiva
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Blood - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Edema: Limb
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
18.6%
11/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Leukocytes
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Lymphatics - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Neutrophils
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Blood and lymphatic system disorders
Platelets
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Cardiac General - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Hypertension
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
35.6%
21/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Hypotension
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Palpitations
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
SupraVentricular arrhythmia, Atrial fibrillation
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
SupraVentricular arrhythmia, Sinus bradycardia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
SupraVentricular arrhythmia, Sinus tachycardia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Cardiac disorders
Ventricular arrhythmia, Ventricular tachycardia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Ear and labyrinth disorders
Auditory/Ear - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Ear and labyrinth disorders
Hearing (without monitoring program)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Ear and labyrinth disorders
Otitis, external
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Endocrine disorders
Hot flashes
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
22.0%
13/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Eye disorders
Blurred vision
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Eye disorders
Diplopia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
37.3%
22/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
23.7%
14/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
50.0%
3/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
11.9%
7/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
2/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.4%
15/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
40.0%
4/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Distension
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
13.6%
8/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Flatulence
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
GI - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Heartburn
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Mucositis (clinical exam), Oral cavity
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Mucositis (functional/symptomatic), Oral cavity
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
18.6%
11/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
50.0%
3/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
40.0%
4/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
28.8%
17/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Taste Alteration
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
22.0%
13/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Constitutional Symptoms - Other
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Fatigue
|
66.7%
2/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
62.5%
5/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
47.5%
28/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
66.7%
4/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
50.0%
5/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Fever
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Insomnia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
18.6%
11/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
40.0%
4/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Abdomen NOS
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Anus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Back
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
22.0%
13/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
66.7%
4/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Bladder
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Buttock
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Chest wall
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Chest/thorax NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Dental/teeth/peridontal
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Extremity - limb
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.4%
15/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
83.3%
5/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
50.0%
5/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Head/headache
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
13.6%
8/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Joint
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.2%
6/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Muscle
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.9%
10/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
66.7%
4/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Neuralgia/peripheral nerve
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Oral cavity
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Other (Specify)
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Pain NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
11.9%
7/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Scalp
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Throat/pharynx/larynx
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Pain, Tumor pain
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Rigors/chills
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Sweating
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.2%
6/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Syndromes - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
General disorders
Weight loss
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Immune system disorders
Allergy - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Immune system disorders
Rhinitis
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Abdomen NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Bladder (urinary)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Lip/perioral
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Neck NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Pharynx
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Upper airway NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection (Documented clinically), Urinary tract NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection with normal ANC, Anal/perianal
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection with normal ANC, Pharynx
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection with normal ANC, Sinus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Infections and infestations
Infection with normal ANC, Upper airway NOS
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
ALT
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
AST
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
11.9%
7/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
11.9%
7/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
50.0%
5/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
CPK
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Cholesterol (serum-high hypercholesteremia)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Creatinine
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.2%
6/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
13.6%
8/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.9%
10/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Lipase
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Metabolic/Lab - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Metabolism and nutrition disorders
Proteinuria
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Gait/walking
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.2%
6/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, Extremity - lower
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
6.8%
4/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
37.5%
3/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy (possibly related to cancer treatment)
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
CNS ischemia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Confusion
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.2%
6/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Mood Alteration, Agitation
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Mood Alteration, Anxiety
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.0%
3/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Mood Alteration, Depression
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neurology - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: Cranial, CN VII Motor-face; Sensory-taste
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
22.0%
13/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: Cranial, CN XI Motor-Sternomastoid And Trapezius
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: Cranial, CN XII Motor-tongue
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: motor
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Neuropathy: sensory
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
22.0%
13/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Nervous system disorders
Somnolence
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Incontinence, urinary
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Renal - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Reproductive system and breast disorders
Gynecomastia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
30.5%
18/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
23.7%
14/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
1.7%
1/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
37.5%
3/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
8.5%
5/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Bruising
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Burn
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Decubitus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis, Radiation
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Dermatology - Other
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.9%
10/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
15.3%
9/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Flushing
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
5.1%
3/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Hand-foot skin reaction
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
39.0%
23/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
33.3%
2/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
40.0%
4/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Hyperpigmentation
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
25.0%
2/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
16.7%
1/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
20.0%
2/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
33.3%
1/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
75.0%
6/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
32.2%
19/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
83.3%
5/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
90.0%
9/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
Hemorrhage pulmonary, Nose
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
12.5%
1/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
3.4%
2/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
Hemorrhage, GI, Anus
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
|
Vascular disorders
Vascular - Other
|
0.00%
0/3 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/8 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/59 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
0.00%
0/6 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
10.0%
1/10 • Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place