Trial Outcomes & Findings for BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma (NCT NCT00727506)
NCT ID: NCT00727506
Last Updated: 2017-08-15
Results Overview
Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
151 participants
Primary outcome timeframe
From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days
Results posted on
2017-08-15
Participant Flow
This study consists of 2 parts (phase I and phase II) with separate participants.
Participant milestones
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
|
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
18
|
39
|
41
|
39
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
8
|
18
|
39
|
41
|
39
|
Reasons for withdrawal
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase II - Temozolomide 75mg/m^2
Patients receiving Temozolomide monotherapy 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
Phase II - Afatinib 40mg
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
|
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
4
|
4
|
1
|
8
|
|
Overall Study
Dose Limiting Toxicity (DLT)
|
2
|
0
|
2
|
0
|
0
|
0
|
|
Overall Study
Progressive disease
|
4
|
7
|
9
|
28
|
38
|
28
|
|
Overall Study
Refused to continue medication
|
0
|
1
|
2
|
3
|
1
|
2
|
|
Overall Study
Other reason not described above
|
0
|
0
|
1
|
4
|
1
|
1
|
Baseline Characteristics
BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma
Baseline characteristics by cohort
| Measure |
Total
n=151 Participants
Total of all reporting groups
|
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase II - Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Temozolomide monotherapy 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
Phase II - Afatinib 40mg
n=41 Participants
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
|
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
n=39 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
56.3 years
STANDARD_DEVIATION 10.3 • n=3 Participants
|
51.7 years
STANDARD_DEVIATION 12.4 • n=99 Participants
|
51.6 years
STANDARD_DEVIATION 14.2 • n=107 Participants
|
51.0 years
STANDARD_DEVIATION 9.4 • n=206 Participants
|
56.9 years
STANDARD_DEVIATION 10.62 • n=7 Participants
|
56.6 years
STANDARD_DEVIATION 9.44 • n=31 Participants
|
55.4 years
STANDARD_DEVIATION 11.02 • n=30 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=3 Participants
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
14 Participants
n=31 Participants
|
18 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
93 Participants
n=3 Participants
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
25 Participants
n=7 Participants
|
27 Participants
n=31 Participants
|
21 Participants
n=30 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Number of participants
n=3 Participants
|
0 Number of participants
n=99 Participants
|
1 Number of participants
n=107 Participants
|
0 Number of participants
n=206 Participants
|
0 Number of participants
n=7 Participants
|
1 Number of participants
n=31 Participants
|
1 Number of participants
n=30 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
6 Number of participants
n=3 Participants
|
0 Number of participants
n=99 Participants
|
0 Number of participants
n=107 Participants
|
2 Number of participants
n=206 Participants
|
2 Number of participants
n=7 Participants
|
0 Number of participants
n=31 Participants
|
2 Number of participants
n=30 Participants
|
|
Race/Ethnicity, Customized
Hawaiian/Pacific Isle
|
1 Number of participants
n=3 Participants
|
0 Number of participants
n=99 Participants
|
0 Number of participants
n=107 Participants
|
0 Number of participants
n=206 Participants
|
0 Number of participants
n=7 Participants
|
0 Number of participants
n=31 Participants
|
1 Number of participants
n=30 Participants
|
|
Race/Ethnicity, Customized
White
|
141 Number of participants
n=3 Participants
|
6 Number of participants
n=99 Participants
|
7 Number of participants
n=107 Participants
|
16 Number of participants
n=206 Participants
|
37 Number of participants
n=7 Participants
|
40 Number of participants
n=31 Participants
|
35 Number of participants
n=30 Participants
|
|
Karnofsky performance score
70
|
33 Number of participants
n=3 Participants
|
1 Number of participants
n=99 Participants
|
1 Number of participants
n=107 Participants
|
1 Number of participants
n=206 Participants
|
9 Number of participants
n=7 Participants
|
9 Number of participants
n=31 Participants
|
12 Number of participants
n=30 Participants
|
|
Karnofsky performance score
80
|
38 Number of participants
n=3 Participants
|
1 Number of participants
n=99 Participants
|
1 Number of participants
n=107 Participants
|
2 Number of participants
n=206 Participants
|
13 Number of participants
n=7 Participants
|
12 Number of participants
n=31 Participants
|
9 Number of participants
n=30 Participants
|
|
Karnofsky performance score
90
|
61 Number of participants
n=3 Participants
|
2 Number of participants
n=99 Participants
|
4 Number of participants
n=107 Participants
|
11 Number of participants
n=206 Participants
|
12 Number of participants
n=7 Participants
|
17 Number of participants
n=31 Participants
|
15 Number of participants
n=30 Participants
|
|
Karnofsky performance score
100
|
19 Number of participants
n=3 Participants
|
2 Number of participants
n=99 Participants
|
2 Number of participants
n=107 Participants
|
4 Number of participants
n=206 Participants
|
5 Number of participants
n=7 Participants
|
3 Number of participants
n=31 Participants
|
3 Number of participants
n=30 Participants
|
PRIMARY outcome
Timeframe: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 daysNumber of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With DLT- Phase I
|
2 participants
|
0 participants
|
4 participants
|
PRIMARY outcome
Timeframe: At six months after randomizationPopulation: Randomised Set (RS). The randomised set includes all patients who were randomised to receive treatment in the Phase II part of the trial.
PFS-6 is defined as probability of patients surviving to six months after randomization without progression. Disease progression was evaluated by an independent review committee and by the investigators, independently. The evaluation by the independent review committee was used for the primary outcome measure. The measurement "Number" the estimated PFS-6 value from the Kaplan-Meier curve of PFS.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Progression-free Survival (PFS-6) at Six Months - Phase II
|
0.230 probablity of survival
Interval 0.09 to 0.37
|
0.030 probablity of survival
Interval 0.0 to 0.09
|
0.103 probablity of survival
Interval 0.0 to 0.21
|
SECONDARY outcome
Timeframe: From treatment start until the date of first documented progression or data cutoff at May 12, 2011, whichever came first, with a mean treatment duration of 69.7 days.Population: Patients treated in Phase I part
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Objective Tumor Response in Phase I
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From randomization to until the date of first documented progression or data cutoff on July 15, 2016, whichever came first, with a mean treatment duration of 110.0 daysPopulation: RS
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review. Only data collected until cut-off date July 15, 2016 were considered.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Objective Tumor Response in Phase II
|
4 participants
Interval 2.9 to 24.2
|
1 participants
Interval 0.1 to 12.9
|
3 participants
Interval 1.6 to 20.9
|
SECONDARY outcome
Timeframe: from date of randomization until the date of first documented progression or death by any cause, whichever came first, assessed up to 9 Months.Population: Randomized set
Progression-free survival was defined as the duration between randomization and the date of the first of the two following events: progression or death.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Progression-free Survival (PFS)- Phase II Part
|
1.87 Months
Interval 1.15 to 3.68
|
0.99 Months
Interval 0.95 to 1.84
|
1.53 Months
Interval 0.99 to 1.87
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24 h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1Population: PKS Set and the patients who had enough PK samples for calculation of AUC. Pharmacokinetic set (PKS) : All patients who provided at least one blood sample were included in the Pharmacokinetic (PK) analysis.
Area under the plasma concentration-time curve of afatinib after multiple administration (AUCτ,ss) of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide (TMZ).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=15 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=5 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
AUCτ,ss for Afatinib
|
1070 ng·h/mL
Standard Deviation 63.7
|
918 ng·h/mL
Standard Deviation 65.3
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1Population: PKS set
maximum measured plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=15 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Cmax,ss for Afatinib
|
63.2 ng/mL
Standard Deviation 62.1
|
50.5 ng/mL
Standard Deviation 58.0
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1Population: PKS set
time from dosing to the maximum plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=15 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Tmax,ss for Afatinib
|
4.00 hour
Full Range 58.0 • Interval 1.5 to 8.0
|
3.50 hour
Full Range 62.1 • Interval 1.0 to 7.92
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1Population: PKS set
Area under the plasma concentration-time curve over the time interval from zero to 08h (AUC (0-8)) of temozolomide in presence and absence of afatinib.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=14 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=17 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
AUC (0-8) for Temozolomide
|
8380 ng·h/mL
Geometric Coefficient of Variation 24.1
|
8160 ng·h/mL
Geometric Coefficient of Variation 27.8
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1Population: PKS set
maximum measured plasma concentration following the first dose of uniform intervals τ (Cmax) of temozolomide in presence and absence of afatinib.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=15 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=17 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Cmax for Temozolomide
|
2520 ng/mL
Geometric Coefficient of Variation 33.3
|
2690 ng/mL
Geometric Coefficient of Variation 39.7
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1Population: PKS set
time from dosing to the maximum plasma concentration following the first dose of uniform intervals τ (tmax) of temozolomide in presence and absence of afatinib.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=15 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=17 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Tmax for Temozolomide
|
1.22 h
Interval 1.0 to 3.25
|
1.00 h
Interval 0.5 to 2.0
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1Population: PKS set
terminal half-life (t1/2) of temozolomide in presence and absence of afatinib
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=14 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=17 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
t1/2 for Temozolomide
|
2.17 hours
Geometric Coefficient of Variation 34.3
|
2.08 hours
Geometric Coefficient of Variation 58.4
|
—
|
SECONDARY outcome
Timeframe: Before (-0.05 h) the drug administration of afatinib on Day 15 of Cycle 2 & 3Population: PKS
Trough plasma concentration of afatinib after multiple administration of 40 mg afatinib administered as monotherapy or in combination with 75 mg/m² temozolomide
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Phase II - Trough Plasma Concentration of Afatinib
predose at Day 15 of Cycle 2 (n=17; 15)
|
19.8 ng/mL
Geometric Coefficient of Variation 69.5 • Interval 0.1 to 12.9
|
29.7 ng/mL
Geometric Coefficient of Variation 72.1 • Interval 1.6 to 20.9
|
—
|
|
Phase II - Trough Plasma Concentration of Afatinib
predose at Day 15 of Cycle 3 (n=10; 10)
|
19.6 ng/mL
Geometric Coefficient of Variation 70.8
|
20.2 ng/mL
Geometric Coefficient of Variation 79.1
|
—
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with the epidermal growth factor receptor variant III (EGFRvIII) assessed by IHC test for the evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFRvIII by immunohistochemistry (IHC) test.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: Negative
|
6 Participants
|
8 Participants
|
5 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: +
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: +/++
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: ++
|
1 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: ++/+++
|
1 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
Sample tested: +++
|
3 Participants
|
5 Participants
|
10 Participants
|
|
Number of Participants With EGFRvIII Assessed by IHC Test.
No Sample for test
|
23 Participants
|
15 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with MGMT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for O6-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry (IHC) test.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With MGMT Marker Assessed by IHC Test.
MGMT+
|
9 Participants
|
8 Participants
|
12 Participants
|
|
Number of Participants With MGMT Marker Assessed by IHC Test.
MGMT-
|
7 Participants
|
15 Participants
|
15 Participants
|
|
Number of Participants With MGMT Marker Assessed by IHC Test.
No Sample for test
|
23 Participants
|
18 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with EGFR marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (IHC) test
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With EGFR Marker Assessed by IHC Test.
EGFR wt+
|
14 Participants
|
23 Participants
|
24 Participants
|
|
Number of Participants With EGFR Marker Assessed by IHC Test.
EGFR wt-
|
2 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With EGFR Marker Assessed by IHC Test.
No Sample for test
|
23 Participants
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with PTEN marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Phosphatase and Tensin Homologue - a tumor suppressor gene/protein (PTEN) by immunohistochemistry (IHC) test.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With PTEN Marker Assessed by IHC Test.
PTEN intact
|
5 Participants
|
4 Participants
|
7 Participants
|
|
Number of Participants With PTEN Marker Assessed by IHC Test.
PTEN loss
|
11 Participants
|
19 Participants
|
21 Participants
|
|
Number of Participants With PTEN Marker Assessed by IHC Test.
No Sample for test
|
23 Participants
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with PAKT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Serinethreonine kinase (PAKT) by immunohistochemistry (IHC) test.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With PAKT Marker Assessed by IHC Test.
PAKT+
|
5 Participants
|
11 Participants
|
11 Participants
|
|
Number of Participants With PAKT Marker Assessed by IHC Test.
PAKT-
|
11 Participants
|
13 Participants
|
16 Participants
|
|
Number of Participants With PAKT Marker Assessed by IHC Test.
No Sample for test
|
23 Participants
|
17 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with EGFR assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFR by fluorescent in situ hybridization (FISH).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With EGFR Assessed by FISH
EGFR abnormal (Amplification)
|
5 Participants
|
14 Participants
|
11 Participants
|
|
Number of Participants With EGFR Assessed by FISH
EGFR normal (Intact)
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With EGFR Assessed by FISH
EGFR abnormal (Gain)
|
10 Participants
|
9 Participants
|
16 Participants
|
|
Number of Participants With EGFR Assessed by FISH
No Sample for test
|
23 Participants
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with PTEN assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for PTEN by fluorescent in situ hybridization (FISH).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With PTEN Assessed by FISH
PTEN abnormal (Loss)
|
11 Participants
|
20 Participants
|
25 Participants
|
|
Number of Participants With PTEN Assessed by FISH
PTEN normal (Gain)
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With PTEN Assessed by FISH
PTEN normal (Intact)
|
4 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With PTEN Assessed by FISH
No Sample for test
|
23 Participants
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with Chromosomes (CEP7) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP7) by fluorescent in situ hybridization (FISH).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Chromosomes (CEP7) Assessed by FISH
CEP7 abnormal (Gain)
|
15 Participants
|
24 Participants
|
27 Participants
|
|
Number of Participants With Chromosomes (CEP7) Assessed by FISH
CEP7 normal (Intact)
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Chromosomes (CEP7) Assessed by FISH
No Sample for test
|
23 Participants
|
17 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (during screening)Population: Randomized set
Number of participants with Chromosomes (CEP10) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP10) by fluorescent in situ hybridization (FISH).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Chromosomes (CEP10) Assessed by FISH
CEP10 abnormal (Loss)
|
10 Participants
|
19 Participants
|
24 Participants
|
|
Number of Participants With Chromosomes (CEP10) Assessed by FISH
CEP10 normal (Gain)
|
2 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Chromosomes (CEP10) Assessed by FISH
CEP10 normal (Intact)
|
4 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Chromosomes (CEP10) Assessed by FISH
No Sample for test
|
23 Participants
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 491 days.Population: Treated set
Safety was assessed based on number of participants with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, All Serious Adverse events (AE) and other significant AEs (according to International Conference on Harmonisation (ICH) E3).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
drug-related AEs
|
4 Participants
|
8 Participants
|
17 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
AEs leading to discontinuation of trial drug
|
2 Participants
|
1 Participants
|
10 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
Serious AE's
|
2 Participants
|
1 Participants
|
10 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
other significant AEs
|
1 Participants
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 491 days.Population: Treated set
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Rash
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Vomiting
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Nausea
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Diarrhoea
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
acne
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Haemorrhage intracranial
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Convulsion
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Syncope
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Hemiparesis
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Aphasia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Brain oedema
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Cerebrovascular accident
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Headache
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Paralysis
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Peroneal nerve palsy
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Vasogenic cerebral oedema
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 491 days.Population: Treated set
Safety of Afatinib assesed based on Number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Grade 1
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Grade 2
|
3 Participants
|
4 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Grade 3
|
0 Participants
|
1 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Grade 4
|
2 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Grade 5
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 491 days.Population: Treated set
Cause of the death reported during on treatment was due to disease progression.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Causes of Death - Phase I
|
0 deaths
|
0 deaths
|
1 deaths
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 518 days.Population: Treated set
Safety was assessed based on number of participants with investigator defined drug-related AEs, AE leading to dose reduction, Adverse events (AEs) leading to discontinuation of trial drug and All Serious Adverse events (SAE).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
drug-related AEs
|
22 Participants
|
35 Participants
|
36 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
AE leading to dose reduction
|
2 Participants
|
4 Participants
|
7 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
AEs leading to discontinuation of trial drug
|
9 Participants
|
8 Participants
|
14 Participants
|
|
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
Serious AE's
|
6 Participants
|
10 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 518 days.Population: Treated set
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Rash
|
3 Participants
|
19 Participants
|
22 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Acne
|
0 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Vomiting
|
8 Participants
|
4 Participants
|
10 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Nausea
|
7 Participants
|
6 Participants
|
13 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Diarrhoea
|
4 Participants
|
29 Participants
|
32 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Neurological decompensation
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Cerebral haemorrhage
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Dysgeusia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Hemiparesis
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Ataxia
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Headache
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Memory impairment
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Speech disorder
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 518 days.Population: Treated set
Safety of Afatinib assessed based on the number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Grade 1
|
3 Participants
|
5 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Grade 2
|
14 Participants
|
18 Participants
|
10 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Grade 3
|
13 Participants
|
15 Participants
|
19 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Grade 4
|
5 Participants
|
2 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Grade 5
|
2 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 518 days.Population: Treated set
Causes of death during on treatment.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Causes of Death - Phase II
Malignant Neoplasm Progression
|
1 deaths
|
0 deaths
|
1 deaths
|
|
Causes of Death - Phase II
Respiratory failure
|
0 deaths
|
0 deaths
|
1 deaths
|
|
Causes of Death - Phase II
Tumor progression
|
1 deaths
|
1 deaths
|
0 deaths
|
SECONDARY outcome
Timeframe: From first administration of treatment until 28 days after last drug administration, up to 518 days.Population: Treated set
Number of participants with Clinically Relevant Abnormalities for decreased Cardiac left ventricular function.
Outcome measures
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=41 Participants
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=39 Participants
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
|---|---|---|---|
|
Number of Participants With Clinically Relevant Abnormalities for Decreased Cardiac Left Ventricular Function - Phase II
|
0.0 Participants
|
0.0 Participants
|
0.0 Participants
|
Adverse Events
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
Serious events: 10 serious events
Other events: 18 other events
Deaths: 0 deaths
Phase II - Temozolomide 75mg/m^2
Serious events: 6 serious events
Other events: 36 other events
Deaths: 0 deaths
Phase II - Afatinib 40mg
Serious events: 10 serious events
Other events: 40 other events
Deaths: 0 deaths
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
Serious events: 13 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 participants at risk
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 participants at risk
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 participants at risk
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase II - Temozolomide 75mg/m^2
n=39 participants at risk
Patients receiving Temozolomide monotherapy 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
Phase II - Afatinib 40mg
n=41 participants at risk
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
|
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
n=39 participants at risk
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Spontaneous haematoma
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Cardiac disorders
Palpitations
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Cellulitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Sepsis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Altered state of consciousness
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Neurological decompensation
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Asthenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
General physical health deterioration
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Pyrexia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Seizure
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Disease progression
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Fatigue
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Aphasia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Convulsion
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Haemorrhage intracranial
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Paralysis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Delirium
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Vascular disorders
Thrombosis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
Other adverse events
| Measure |
Phase I - Afatinib 20 mg Plus Temozolomide 75mg/m^2
n=6 participants at risk
Patients receiving Afatinib 20mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 40 mg Plus Temozolomide 75mg/m^2
n=8 participants at risk
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase I - Afatinib 50 mg Plus Temozolomide 75mg/m^2
n=18 participants at risk
Patients receiving Afatinib 50mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase I part
|
Phase II - Temozolomide 75mg/m^2
n=39 participants at risk
Patients receiving Temozolomide monotherapy 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part
|
Phase II - Afatinib 40mg
n=41 participants at risk
Patients receiving Afatinib monotherapy 40mg once daily (q.d.) - Phase II part
|
Phase II - Afatinib 40mg Plus Temozolomide 75 mg/m^2
n=39 participants at risk
Patients receiving Afatinib 40mg once daily (q.d.) plus Temozolomide 75 mg/m\^2 for 21 days followed by 7 days off - Phase II part.
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Influenza
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Depression
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.8%
5/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
17.9%
7/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
15.4%
6/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.8%
5/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
14.6%
6/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
23.1%
9/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.8%
5/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
87.5%
7/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
72.2%
13/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
43.9%
18/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
56.4%
22/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Asthenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Chills
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Fatigue
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
50.0%
9/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.6%
10/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
22.0%
9/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
28.2%
11/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Gait disturbance
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Mucosal inflammation
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Oedema peripheral
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Temperature intolerance
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.8%
5/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Ear and labyrinth disorders
Deafness bilateral
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Eye disorders
Dry eye
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Eye disorders
Eye pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Eye disorders
Vision blurred
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
22.2%
4/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
17.9%
7/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
50.0%
4/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
72.2%
13/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
70.7%
29/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
79.5%
31/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
20.5%
8/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
14.6%
6/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
33.3%
13/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
38.9%
7/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
20.5%
8/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
20.5%
8/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Infection
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Localised infection
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Paronychia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Rash pustular
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
15.4%
6/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Weight decreased
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
17.9%
7/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Weight increased
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
28.2%
11/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
27.8%
5/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.0%
2/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
38.9%
7/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Increased appetite
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
17.9%
7/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Amnesia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Aphasia
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
15.4%
6/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.8%
5/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.6%
10/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
14.6%
6/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
25.6%
10/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Hemiparesis
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
15.4%
6/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Motor dysfunction
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
10.3%
4/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Somnolence
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
9.8%
4/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Tremor
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.3%
3/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Seizure
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
22.0%
9/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
7.7%
3/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Sensory disturbance
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.1%
2/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Endocrine disorders
Hypothyroidism
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
4.9%
2/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Dyschezia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Flatulence
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Oral discomfort
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Gastrointestinal disorders
Tongue discolouration
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Feeling cold
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Irritability
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Malaise
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Oedema
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Pyrexia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
General disorders
Thirst
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Candidiasis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Cellulitis
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Rhinovirus infection
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Lipase increased
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
Liver function test abnormal
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Investigations
White blood cells urine
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Ataxia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Convulsion
|
33.3%
2/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
16.7%
3/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Hemianopia
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Lethargy
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Mental impairment
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Sedation
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Syncope
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Nervous system disorders
Vasogenic cerebral oedema
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Affect lability
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Reproductive system and breast disorders
Genital discomfort
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Reproductive system and breast disorders
Vulvovaginal discomfort
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
16.7%
1/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
11.1%
2/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.4%
1/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
12.5%
1/8 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
5.6%
1/18 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
0.00%
0/41 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
2.6%
1/39 • From first administration of treatment until 28 days after last drug administration, up to 491 days (Phase I) and 518 days (Phase II).
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER