Trial Outcomes & Findings for Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib) (NCT NCT01976741)
NCT ID: NCT01976741
Last Updated: 2021-05-06
Results Overview
The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
168 participants
Primary outcome timeframe
Up to 21 days
Results posted on
2021-05-06
Participant Flow
Study was conducted at 29 centers in 7 countries, between 30 Dec 2013 (first subject first visit) and 27 Nov 2019 (last subject last visit).
A total of 988 participants were screened, of whom 168 participants were assigned into the study and received at least one dose of study medication.
Participant milestones
| Measure |
Rogaratinib 50 mg BID
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 100 mg BID
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
4
|
3
|
4
|
4
|
23
|
74
|
8
|
40
|
|
Overall Study
COMPLETED
|
3
|
4
|
1
|
2
|
4
|
4
|
19
|
62
|
7
|
36
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
3
|
1
|
0
|
0
|
4
|
12
|
1
|
4
|
Reasons for withdrawal
| Measure |
Rogaratinib 50 mg BID
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 100 mg BID
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
1
|
0
|
0
|
1
|
4
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
2
|
0
|
0
|
0
|
3
|
8
|
1
|
4
|
Baseline Characteristics
Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib)
Baseline characteristics by cohort
| Measure |
Rogaratinib 50 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 50 mg solution on C1D1 and 50 mg solution BID (in total 100 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 100 mg BID
n=4 Participants
Participants received a single dose of 100 mg Rogaratinib tablet formulation on C1D-3, followed by a single dose of 100 mg solution on C1D1 and continued with 100 mg BID of solution (in total 200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 200 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib Dose Expansion (All Comers)
n=23 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=74 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=8 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=40 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Total
n=168 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
52.5 Years
STANDARD_DEVIATION 20.4 • n=5 Participants
|
58.5 Years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
55.8 Years
STANDARD_DEVIATION 15.3 • n=5 Participants
|
56.3 Years
STANDARD_DEVIATION 9.8 • n=4 Participants
|
56.8 Years
STANDARD_DEVIATION 12.9 • n=21 Participants
|
64.3 Years
STANDARD_DEVIATION 8.4 • n=8 Participants
|
63.0 Years
STANDARD_DEVIATION 7.8 • n=8 Participants
|
66.4 Years
STANDARD_DEVIATION 8.6 • n=24 Participants
|
63.4 Years
STANDARD_DEVIATION 11.1 • n=42 Participants
|
62.6 Years
STANDARD_DEVIATION 6.6 • n=42 Participants
|
63.6 Years
STANDARD_DEVIATION 9.3 • n=42 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
20 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
8 Participants
n=42 Participants
|
46 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
14 Participants
n=8 Participants
|
54 Participants
n=24 Participants
|
8 Participants
n=42 Participants
|
32 Participants
n=42 Participants
|
122 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
23 Participants
n=8 Participants
|
61 Participants
n=24 Participants
|
8 Participants
n=42 Participants
|
34 Participants
n=42 Participants
|
149 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
12 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
6 Participants
n=42 Participants
|
18 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
13 Participants
n=24 Participants
|
1 Participants
n=42 Participants
|
11 Participants
n=42 Participants
|
37 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
15 Participants
n=8 Participants
|
50 Participants
n=24 Participants
|
7 Participants
n=42 Participants
|
22 Participants
n=42 Participants
|
113 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
11 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
7 Participants
n=42 Participants
|
18 Participants
n=42 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance status
ECOG=0
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
10 Participants
n=8 Participants
|
20 Participants
n=24 Participants
|
3 Participants
n=42 Participants
|
14 Participants
n=42 Participants
|
56 Participants
n=42 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance status
ECOG=1
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
49 Participants
n=24 Participants
|
5 Participants
n=42 Participants
|
22 Participants
n=42 Participants
|
100 Participants
n=42 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance status
ECOG=2
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
5 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
12 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Up to 21 daysPopulation: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%
|
800 mg BID
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 21 daysPopulation: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.
DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of DLTs During Cycle 1
|
0 DLTs
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid pharmacokinetic (PK) data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
2760 µg/L
Geometric Coefficient of Variation 56.5
|
11300 µg/L
Geometric Coefficient of Variation 33.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
3640 µg/L
Geometric Coefficient of Variation 16.8
|
4360 µg/L
Geometric Coefficient of Variation 36.4
|
5630 µg/L
Geometric Coefficient of Variation 46.2
|
9480 µg/L
Geometric Coefficient of Variation 16.1
|
9060 µg/L
Geometric Coefficient of Variation 32.3
|
10200 µg/L
Geometric Coefficient of Variation 17.3
|
11000 µg/L
Geometric Coefficient of Variation 34.3
|
11000 µg/L
Geometric Coefficient of Variation 47.6
|
10900 µg/L
Geometric Coefficient of Variation 32.5
|
11000 µg/L
Geometric Coefficient of Variation 48.1
|
13900 µg/L
Geometric Coefficient of Variation 52.6
|
11200 µg/L
Geometric Coefficient of Variation 26.0
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
15600 µg*h/L
Geometric Coefficient of Variation 72.0
|
71000 µg*h/L
Geometric Coefficient of Variation 42.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
12100 µg*h/L
Geometric Coefficient of Variation 16.3
|
15300 µg*h/L
Geometric Coefficient of Variation 41.4
|
33200 µg*h/L
Geometric Coefficient of Variation 33.1
|
44000 µg*h/L
Geometric Coefficient of Variation 68.9
|
54300 µg*h/L
Geometric Coefficient of Variation 31.3
|
55700 µg*h/L
Geometric Coefficient of Variation 43.5
|
63900 µg*h/L
Geometric Coefficient of Variation 45.0
|
74200 µg*h/L
Geometric Coefficient of Variation 49.7
|
63700 µg*h/L
Geometric Coefficient of Variation 46.5
|
59700 µg*h/L
Geometric Coefficient of Variation 56.4
|
101000 µg*h/L
Geometric Coefficient of Variation 37.4
|
66700 µg*h/L
Geometric Coefficient of Variation 32.0
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
20000 µg*h/L
Geometric Coefficient of Variation 87.3
|
99300 µg*h/L
Geometric Coefficient of Variation 52.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ \[lower limit of quantification\] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=49 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=11 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
14200 µg*h/L
Geometric Coefficient of Variation 24.4
|
20100 µg*h/L
Geometric Coefficient of Variation 57.7
|
43800 µg*h/L
Geometric Coefficient of Variation 36.3
|
62000 µg*h/L
Geometric Coefficient of Variation 114
|
78000 µg*h/L
Geometric Coefficient of Variation 38.5
|
86600 µg*h/L
Geometric Coefficient of Variation 41.2
|
103000 µg*h/L
Geometric Coefficient of Variation 53.5
|
121000 µg*h/L
Geometric Coefficient of Variation 49.3
|
104000 µg*h/L
Geometric Coefficient of Variation 73.4
|
108000 µg*h/L
Geometric Coefficient of Variation 33.8
|
172000 µg*h/L
Geometric Coefficient of Variation 55.3
|
94900 µg*h/L
Geometric Coefficient of Variation 39.6
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
20200 µg*h/L
Geometric Coefficient of Variation 87.1
|
102000 µg*h/L
Geometric Coefficient of Variation 55.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=46 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=18 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=11 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=12 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
14300 µg*h/L
Geometric Coefficient of Variation 24.5
|
20700 µg*h/L
Geometric Coefficient of Variation 58.1
|
44300 µg*h/L
Geometric Coefficient of Variation 37.1
|
64000 µg*h/L
Geometric Coefficient of Variation 118
|
79800 µg*h/L
Geometric Coefficient of Variation 39.5
|
95400 µg*h/L
Geometric Coefficient of Variation 48.7
|
109000 µg*h/L
Geometric Coefficient of Variation 58.4
|
133000 µg*h/L
Geometric Coefficient of Variation 53.3
|
109000 µg*h/L
Geometric Coefficient of Variation 77.5
|
115000 µg*h/L
Geometric Coefficient of Variation 38.9
|
191000 µg*h/L
Geometric Coefficient of Variation 69.9
|
99600 µg*h/L
Geometric Coefficient of Variation 46.5
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
0.0276 /L
Geometric Coefficient of Variation 56.5
|
0.0141 /L
Geometric Coefficient of Variation 33.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
0.0728 /L
Geometric Coefficient of Variation 16.8
|
0.0436 /L
Geometric Coefficient of Variation 36.4
|
0.0282 /L
Geometric Coefficient of Variation 46.2
|
0.0237 /L
Geometric Coefficient of Variation 16.1
|
0.0151 /L
Geometric Coefficient of Variation 32.3
|
0.0127 /L
Geometric Coefficient of Variation 17.3
|
0.0138 /L
Geometric Coefficient of Variation 34.3
|
0.0137 /L
Geometric Coefficient of Variation 47.6
|
0.0137 /L
Geometric Coefficient of Variation 32.5
|
0.0137 /L
Geometric Coefficient of Variation 48.1
|
0.0174 /L
Geometric Coefficient of Variation 52.6
|
0.0140 /L
Geometric Coefficient of Variation 26.0
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
0.156 h/L
Geometric Coefficient of Variation 72.0
|
0.0888 h/L
Geometric Coefficient of Variation 42.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
0.242 h/L
Geometric Coefficient of Variation 16.3
|
0.153 h/L
Geometric Coefficient of Variation 41.4
|
0.166 h/L
Geometric Coefficient of Variation 33.1
|
0.110 h/L
Geometric Coefficient of Variation 68.9
|
0.0906 h/L
Geometric Coefficient of Variation 31.1
|
0.0696 h/L
Geometric Coefficient of Variation 43.5
|
0.0798 h/L
Geometric Coefficient of Variation 45.0
|
0.0927 h/L
Geometric Coefficient of Variation 49.7
|
0.0796 h/L
Geometric Coefficient of Variation 46.5
|
0.0747 h/L
Geometric Coefficient of Variation 56.4
|
0.126 h/L
Geometric Coefficient of Variation 37.4
|
0.0834 h/L
Geometric Coefficient of Variation 32.0
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
0.200 h/L
Geometric Coefficient of Variation 87.3
|
0.124 h/L
Geometric Coefficient of Variation 52.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Area under the plasma concentration vs time curve from time zero to the last data point \> LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=49 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=11 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
0.283 h/L
Geometric Coefficient of Variation 24.4
|
0.201 h/L
Geometric Coefficient of Variation 57.7
|
0.219 h/L
Geometric Coefficient of Variation 36.3
|
0.155 h/L
Geometric Coefficient of Variation 114
|
0.130 h/L
Geometric Coefficient of Variation 38.5
|
0.108 h/L
Geometric Coefficient of Variation 41.2
|
0.129 h/L
Geometric Coefficient of Variation 53.5
|
0.152 h/L
Geometric Coefficient of Variation 49.3
|
0.130 h/L
Geometric Coefficient of Variation 73.4
|
0.135 h/L
Geometric Coefficient of Variation 33.8
|
0.215 h/L
Geometric Coefficient of Variation 55.3
|
0.119 h/L
Geometric Coefficient of Variation 39.6
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)Population: All participants with valid PK data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
|
0.202 h/L
Geometric Coefficient of Variation 87.1
|
0.127 h/L
Geometric Coefficient of Variation 55.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)Population: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=46 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=18 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=11 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=12 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
|
0.286 h/L
Geometric Coefficient of Variation 24.5
|
0.207 h/L
Geometric Coefficient of Variation 58.1
|
0.221 h/L
Geometric Coefficient of Variation 37.1
|
0.160 h/L
Geometric Coefficient of Variation 118
|
0.133 h/L
Geometric Coefficient of Variation 39.5
|
0.119 h/L
Geometric Coefficient of Variation 48.7
|
0.137 h/L
Geometric Coefficient of Variation 58.4
|
0.166 h/L
Geometric Coefficient of Variation 53.3
|
0.136 h/L
Geometric Coefficient of Variation 77.5
|
0.144 h/L
Geometric Coefficient of Variation 38.9
|
0.239 h/L
Geometric Coefficient of Variation 69.9
|
0.124 h/L
Geometric Coefficient of Variation 46.5
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
3940 µg/L
Geometric Coefficient of Variation 38.5
|
4870 µg/L
Geometric Coefficient of Variation 35.2
|
8320 µg/L
Geometric Coefficient of Variation 68.9
|
9490 µg/L
Geometric Coefficient of Variation 63.1
|
10500 µg/L
Geometric Coefficient of Variation 32.6
|
12400 µg/L
Geometric Coefficient of Variation 33.8
|
12600 µg/L
Geometric Coefficient of Variation 34.6
|
11000 µg/L
Geometric Coefficient of Variation 27.9
|
12300 µg/L
Geometric Coefficient of Variation 31.0
|
13100 µg/L
Geometric Coefficient of Variation 33.6
|
13100 µg/L
|
12300 µg/L
Geometric Coefficient of Variation 40.5
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
0.0789 /L
Geometric Coefficient of Variation 38.5
|
0.0487 /L
Geometric Coefficient of Variation 35.2
|
0.0416 /L
Geometric Coefficient of Variation 68.9
|
0.0237 /L
Geometric Coefficient of Variation 63.1
|
0.0174 /L
Geometric Coefficient of Variation 32.6
|
0.0155 /L
Geometric Coefficient of Variation 33.8
|
0.0158 /L
Geometric Coefficient of Variation 34.6
|
0.0138 /L
Geometric Coefficient of Variation 27.9
|
0.0154 /L
Geometric Coefficient of Variation 31.0
|
0.0163 /L
Geometric Coefficient of Variation 33.6
|
0.0163 /L
|
0.0153 /L
Geometric Coefficient of Variation 40.5
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=69 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=22 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
13300 µg*h/L
Geometric Coefficient of Variation 75.4
|
21500 µg*h/L
Geometric Coefficient of Variation 98.5
|
41700 µg*h/L
Geometric Coefficient of Variation 27.9
|
61100 µg*h/L
Geometric Coefficient of Variation 66.2
|
73500 µg*h/L
Geometric Coefficient of Variation 33.4
|
90900 µg*h/L
Geometric Coefficient of Variation 28.8
|
85300 µg*h/L
Geometric Coefficient of Variation 42.8
|
87100 µg*h/L
Geometric Coefficient of Variation 28.5
|
81700 µg*h/L
Geometric Coefficient of Variation 44.5
|
84500 µg*h/L
Geometric Coefficient of Variation 40.8
|
106000 µg*h/L
|
87100 µg*h/L
Geometric Coefficient of Variation 49.1
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=69 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=22 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
0.266 h/L
Geometric Coefficient of Variation 75.4
|
0.215 h/L
Geometric Coefficient of Variation 98.5
|
0.209 h/L
Geometric Coefficient of Variation 27.9
|
0.153 h/L
Geometric Coefficient of Variation 66.2
|
0.123 h/L
Geometric Coefficient of Variation 33.4
|
0.114 h/L
Geometric Coefficient of Variation 28.8
|
0.107 h/L
Geometric Coefficient of Variation 42.8
|
0.109 h/L
Geometric Coefficient of Variation 28.5
|
0.102 h/L
Geometric Coefficient of Variation 44.5
|
0.106 h/L
Geometric Coefficient of Variation 40.8
|
0.132 h/L
|
0.109 h/L
Geometric Coefficient of Variation 49.1
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15
|
12500 µg*h/L
Geometric Coefficient of Variation 78.5
|
21500 µg*h/L
Geometric Coefficient of Variation 99.8
|
39200 µg*h/L
Geometric Coefficient of Variation 19.1
|
60200 µg*h/L
Geometric Coefficient of Variation 65.8
|
72500 µg*h/L
Geometric Coefficient of Variation 33.3
|
89000 µg*h/L
Geometric Coefficient of Variation 30.9
|
81500 µg*h/L
Geometric Coefficient of Variation 43.4
|
84100 µg*h/L
Geometric Coefficient of Variation 31.3
|
75000 µg*h/L
Geometric Coefficient of Variation 44.3
|
83600 µg*h/L
Geometric Coefficient of Variation 40.8
|
103000 µg*h/L
|
81300 µg*h/L
Geometric Coefficient of Variation 50.1
|
PRIMARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
0.250 h/L
Geometric Coefficient of Variation 78.5
|
0.215 h/L
Geometric Coefficient of Variation 99.8
|
0.196 h/L
Geometric Coefficient of Variation 19.1
|
0.151 h/L
Geometric Coefficient of Variation 65.8
|
0.121 h/L
Geometric Coefficient of Variation 33.3
|
0.111 h/L
Geometric Coefficient of Variation 30.9
|
0.102 h/L
Geometric Coefficient of Variation 43.4
|
0.105 h/L
Geometric Coefficient of Variation 31.3
|
0.0937 h/L
Geometric Coefficient of Variation 44.3
|
0.105 h/L
Geometric Coefficient of Variation 40.8
|
0.129 h/L
|
0.102 h/L
Geometric Coefficient of Variation 50.1
|
PRIMARY outcome
Timeframe: On Cycle1, Day 1Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
%AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=13 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
%AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877
|
0.164 percentage
Interval 0.0363 to 0.665
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: On Cycle1, Day 1Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
%AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=13 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
%AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877
|
0.180 percentage
Interval 0.0587 to 0.695
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: On Cycle1, Day 1Population: Urine interval samples on C1D1 were collected in a subgroup of subjects from the 800 mg BID expansion part.
%AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=13 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
%AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877
|
0.0224 percentage
Interval 0.0107 to 0.0596
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Response as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1: complete response (CR: disappearance of all target lesions), partial response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as the reference the baseline sum of diameters), stable disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum of diameters while in the trial), progressive disease (PD: at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study).
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=22 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=70 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=7 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=37 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
missing
|
2 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
CR
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
SD
|
10 Participants
|
12 Participants
|
34 Participants
|
2 Participants
|
22 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
PD
|
9 Participants
|
8 Participants
|
20 Participants
|
3 Participants
|
11 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
PR
|
0 Participants
|
1 Participants
|
14 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
PFS was defined as the time (days) from the date of the first dose of study drug to the date of the first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented. PFS for participants without tumor progression at the time of analysis was censored at their last date of tumor evaluation.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=22 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=70 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=7 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=37 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Progression-free Survival (PFS)
|
45 Days
Interval 41.0 to 88.0
|
47 Days
Interval 38.0 to 231.0
|
105 Days
Interval 80.0 to 109.0
|
44 Days
Interval 24.0 to 144.0
|
84 Days
Interval 50.0 to 100.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
TTP was defined as the time from start of study treatment until first observed disease progression (radiological or clinical). Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=22 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=70 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=7 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=37 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Progression (TTP)
|
45 Days
Interval 41.0 to 76.0
|
47 Days
Interval 38.0 to 231.0
|
105 Days
Interval 80.0 to 109.0
|
68 Days
Interval 35.0 to 295.0
|
85 Days
Interval 50.0 to 105.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Participants with a documented objective response of PR or CR.
DOR (for partial and complete response (PR/CR)) was defined as the time (days) from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). DOR was calculated for responders only, i.e. participants with complete or partial response. Therefore, the dose escalation group is not displayed.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=1 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=15 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=1 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=2 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Response (DOR)
|
522 Days
Not Calculated
|
126 Days
Interval 63.0 to 464.0
|
105 Days
Not Calculated
|
225 Days
Interval 65.0 to 385.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have post-baseline efficacy data available. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=22 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=70 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=7 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=37 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Treatment (DOT)
|
51 Days
Interval 39.0 to 80.0
|
82 Days
Interval 43.0 to 126.0
|
106 Days
Interval 86.0 to 119.0
|
49 Days
Interval 12.0 to 147.0
|
84 Days
Interval 51.0 to 119.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline to C2D1Population: All participants with FGF23 data available, and participants from expansion groups were combined as pre-specified in the Statistical Analysis Plan.
Change in serum FGF23 levels from baseline to C2D1 was reported as ratio to baseline (%).
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=2 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=1 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=2 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=2 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=48 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1
|
201.5 Ratio to baseline (%)
Standard Deviation 106.3
|
149.9 Ratio to baseline (%)
|
441.9 Ratio to baseline (%)
Standard Deviation 346.2
|
528.0 Ratio to baseline (%)
Standard Deviation 290.4
|
402.2 Ratio to baseline (%)
Standard Deviation 35.2
|
517.7 Ratio to baseline (%)
Standard Deviation 261.0
|
487.0 Ratio to baseline (%)
Standard Deviation 447.7
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=18 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=17 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=62 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=6 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=33 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study
|
8.22 beats per minute
Standard Deviation 12.47
|
6.41 beats per minute
Standard Deviation 15.60
|
6.40 beats per minute
Standard Deviation 14.40
|
1.42 beats per minute
Standard Deviation 11.65
|
6.27 beats per minute
Standard Deviation 15.02
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to 2 yearsPopulation: Participants received at least one dose of Rogaratinib and have valid data for this outcome measure. Participants were grouped as described in the SAP to allow a comparison of all dose escalation patients (all dose levels pooled together), dose expansion patients (four groups) and total number of patients (overview summaries) in the same table.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=18 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=17 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=62 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=6 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=33 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Systolic Blood Pressure
|
-1.33 mmHg
Standard Deviation 16.44
|
-4.65 mmHg
Standard Deviation 16.73
|
-2.56 mmHg
Standard Deviation 19.45
|
-5.00 mmHg
Standard Deviation 12.37
|
-1.83 mmHg
Standard Deviation 18.85
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Diastolic Blood Pressure
|
-2.50 mmHg
Standard Deviation 13.50
|
-4.76 mmHg
Standard Deviation 6.99
|
-0.63 mmHg
Standard Deviation 12.08
|
-0.58 mmHg
Standard Deviation 9.23
|
0.41 mmHg
Standard Deviation 12.55
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to Cycle 1, Day 15Population: Safety Analysis Set (SAF): All participants who received at least one dose of the study medication, and valid data for this outcome measure, and participants from dose escalation groups were combined as pre-specified in the Statistical Analysis Plan.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=21 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=22 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=19 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=6 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=18 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15
|
0.60 msec
Standard Deviation 23.11
|
12.86 msec
Standard Deviation 24.16
|
7.82 msec
Standard Deviation 29.39
|
2.89 msec
Standard Deviation 16.47
|
6.41 msec
Standard Deviation 21.14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: On Cycle 1, Day -3 and Cycle 1, Day 1Population: Only participants who received both tablet and solution formulation were included in the analysis.
In order to evaluate the relative bioavailability of the tablet formulation, tablet Cmax/D, AUC(0-tlast)/D, and AUC/D on Cycle 1, Day -3 were compared to solution Cmax/D, AUC(0-tlast)/D, AUC/D on Cycle 1, Day 1 for all analytes. The logarithms of the PK parameters were analyzed using analysis of variance (ANOVA) including participant and formulation effects. Based on these analyses, point estimates (LS-means) and exploratory 90% confidence intervals for the ratios (tablet/solution) of Cmax/D, AUC(0- tlast)/D, and AUC/D were calculated by re-transformation of the logarithmic data using the intra-individual standard deviation of the ANOVA.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
AUC(0-tlast)/D
|
0.9945 ratio
Interval 0.7698 to 1.2847
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
AUC/D
|
0.9776 ratio
Interval 0.7609 to 1.2561
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
Cmax/D
|
0.6335 ratio
Interval 0.4343 to 0.924
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dosePopulation: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Tmax (time to reach maximum drug concentration in plasma) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day 1
|
0.633 hours
Interval 0.55 to 0.983
|
0.783 hours
Interval 0.533 to 0.983
|
1.02 hours
Interval 0.617 to 3.25
|
1.02 hours
Interval 1.0 to 1.08
|
1.54 hours
Interval 1.08 to 2.07
|
2.53 hours
Interval 0.517 to 4.05
|
2.00 hours
Interval 0.483 to 4.05
|
2.00 hours
Interval 0.517 to 8.0
|
2.00 hours
Interval 0.5 to 3.25
|
1.00 hours
Interval 0.483 to 2.0
|
1.28 hours
Interval 0.517 to 2.05
|
2.02 hours
Interval 0.5 to 4.0
|
|
Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day -3
|
NA hours
No data at the time point
|
2.02 hours
Interval 0.983 to 3.03
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
2.99 hours
Interval 1.0 to 6.0
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
SECONDARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dosePopulation: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Tlast (time of last plasma concentration above LLOQ) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=51 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=11 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=19 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=13 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=13 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day -3
|
NA hours
No data at the time point
|
48.1 hours
Interval 47.9 to 48.4
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
48.0 hours
Interval 46.6 to 48.3
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
NA hours
No data at the time point
|
|
Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day 1
|
47.7 hours
Interval 46.4 to 47.8
|
47.9 hours
Interval 23.9 to 48.3
|
47.9 hours
Interval 6.0 to 48.6
|
46.9 hours
Interval 24.1 to 48.0
|
48.0 hours
Interval 47.7 to 48.1
|
47.9 hours
Interval 47.8 to 49.5
|
47.9 hours
Interval 11.6 to 49.5
|
47.6 hours
Interval 8.0 to 48.2
|
47.9 hours
Interval 45.9 to 48.5
|
48.0 hours
Interval 11.6 to 49.5
|
48.2 hours
Interval 48.1 to 48.3
|
47.8 hours
Interval 12.0 to 48.7
|
SECONDARY outcome
Timeframe: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dosePopulation: All participants with valid PK data on Cycle 1, Day -3 and on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
T1/2 (half-life associated with the terminal slope) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=3 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=4 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=46 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=10 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=18 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=11 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=2 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=12 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day -3
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
8.15 hours
Geometric Coefficient of Variation 22.3
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
8.22 hours
Geometric Coefficient of Variation 31.6
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
NA hours
Geometric Coefficient of Variation NA
No data at the time point
|
|
T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Cycle 1, Day 1
|
8.34 hours
Geometric Coefficient of Variation 24.9
|
8.93 hours
Geometric Coefficient of Variation 40.2
|
7.51 hours
Geometric Coefficient of Variation 19.2
|
7.93 hours
Geometric Coefficient of Variation 54.2
|
8.51 hours
Geometric Coefficient of Variation 29.4
|
9.29 hours
Geometric Coefficient of Variation 9.86
|
11.7 hours
Geometric Coefficient of Variation 44.3
|
12.5 hours
Geometric Coefficient of Variation 38.7
|
12.3 hours
Geometric Coefficient of Variation 52.1
|
11.5 hours
Geometric Coefficient of Variation 42.7
|
14.1 hours
Geometric Coefficient of Variation 57.7
|
11.4 hours
Geometric Coefficient of Variation 41.0
|
SECONDARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) of BAY1163877. Median and full range were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
0.80 hours
Interval 0.5 to 1.1
|
1.08 hours
Interval 0.5 to 1.13
|
1.12 hours
Interval 1.05 to 4.02
|
2.08 hours
Interval 0.5 to 2.17
|
2.10 hours
Interval 2.0 to 3.08
|
2.56 hours
Interval 1.05 to 5.53
|
2.00 hours
Interval 0.0 to 5.53
|
3.17 hours
Interval 1.0 to 4.03
|
1.98 hours
Interval 0.5 to 4.0
|
1.98 hours
Interval 0.5 to 4.07
|
2.07 hours
Interval 2.07 to 2.07
|
2.00 hours
Interval 0.0 to 4.0
|
SECONDARY outcome
Timeframe: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dosePopulation: All participants with valid PK data on Cycle 1, Day 15. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.
Tlast,md (time of last plasma concentration above LLOQ after multiple-dose administration) of BAY1163877. Median and full range were reported.
Outcome measures
| Measure |
Rogaratinib Total Dose Escalation
n=4 Participants
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Expansion Food Effect
n=3 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib 200 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 200 mg tablet on C1D1 and 200 mg tablet BID (in total 400 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 400 mg BID
n=3 Participants
Participants received Rogaratinib as a single dose of 400 mg tablet on C1D1 and 400 mg tablet BID (in total 800 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 600 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 600 mg tablet on C1D1 and 600 mg tablet BID (in total 1200 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID
n=4 Participants
Participants received Rogaratinib as a single dose of 800 mg tablet on C1D1 and 800 mg tablet BID (in total 1600 mg) from C1D3 ongoing in 21-days cycles in dose escalation phase.
|
Rogaratinib 800 mg BID Pooled
n=70 Participants
Participants received Rogaratinib 800 mg tablet BID (in total 1600 mg) in dose escalation phase and MTD expansion phase.
|
Rogaratinib Expansion Food Effect
n=7 Participants
For food effect assessment, participants in the MTD expansion cohorts (1600 mg) of study Part 1 and Part 2 received single doses (800 mg) of the study drug on C1D-3 (after consumption of a high-fat, high-calorie breakfast) and on C1D1 (after an overnight fast of at least 8 h). The participants continued with 800 mg BID doses of the study drug from C1D3 onward.
|
Rogaratinib Dose Expansion (All Comers)
n=15 Participants
Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=27 Participants
Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=1 Participants
Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=23 Participants
Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
|
9.80 hours
Interval 6.08 to 11.8
|
11.7 hours
Interval 11.6 to 12.3
|
11.6 hours
Interval 8.0 to 12.6
|
11.7 hours
Interval 11.5 to 11.7
|
11.6 hours
Interval 11.5 to 11.8
|
11.7 hours
Interval 11.1 to 12.0
|
11.7 hours
Interval 6.0 to 12.4
|
11.7 hours
Interval 8.62 to 12.1
|
11.5 hours
Interval 7.83 to 12.0
|
12.0 hours
Interval 8.4 to 12.4
|
11.4 hours
Interval 11.4 to 11.4
|
11.7 hours
Interval 6.0 to 12.0
|
Adverse Events
Rogaratinib Total Dose Escalation
Serious events: 9 serious events
Other events: 22 other events
Deaths: 3 deaths
Rogaratinib Dose Expansion (All Comers)
Serious events: 14 serious events
Other events: 23 other events
Deaths: 6 deaths
Rogaratinib Dose Expansion (BC)
Serious events: 44 serious events
Other events: 73 other events
Deaths: 17 deaths
Rogaratinib Dose Expansion (SCCHN)
Serious events: 5 serious events
Other events: 8 other events
Deaths: 2 deaths
Rogaratinib Dose Expansion (sqNSCLC)
Serious events: 24 serious events
Other events: 40 other events
Deaths: 12 deaths
Serious adverse events
| Measure |
Rogaratinib Total Dose Escalation
n=23 participants at risk
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Dose Expansion (All Comers)
n=23 participants at risk
Subjects with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=74 participants at risk
Subjects with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=8 participants at risk
Subjects with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=40 participants at risk
Subjects with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|
|
Infections and infestations
Herpes zoster
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Retinopathy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Chronic gastritis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Dysphagia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Ileus
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Subileus
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Death
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Fatigue
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Pyrexia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Sudden death
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
General physical health deterioration
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Kidney infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Pneumonia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Sepsis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Septic shock
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Injury, poisoning and procedural complications
Tracheal obstruction
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Amylase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Lipase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
4.3%
1/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Neck mass
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pharyngeal cancer
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Seizure
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Spinal cord oedema
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Dural arteriovenous fistula
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Azotaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Renal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Bladder tamponade
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Reproductive system and breast disorders
Perineal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.0%
3/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal stenosis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Surgical and medical procedures
Nephrostomy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Hypotension
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Peripheral vascular disorder
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Arterial haemorrhage
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
Other adverse events
| Measure |
Rogaratinib Total Dose Escalation
n=23 participants at risk
Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
|
Rogaratinib Dose Expansion (All Comers)
n=23 participants at risk
Subjects with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (BC)
n=74 participants at risk
Subjects with bladder cancer (BC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (SCCHN)
n=8 participants at risk
Subjects with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
Rogaratinib Dose Expansion (sqNSCLC)
n=40 participants at risk
Subjects with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet BID (1600 mg/day) in 21-days cycles.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Stomatitis
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
14.9%
11/74 • Number of events 18 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
20.0%
8/40 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.6%
13/74 • Number of events 18 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
15.0%
6/40 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Asthenia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
18.9%
14/74 • Number of events 35 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Chest pain
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.4%
4/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Fatigue
|
30.4%
7/23 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
30.4%
7/23 • Number of events 12 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
37.8%
28/74 • Number of events 55 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
27.5%
11/40 • Number of events 22 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Oedema
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Oedema peripheral
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
General disorders
Pyrexia
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
26.1%
6/23 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
15.0%
6/40 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Bronchitis
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Nasopharyngitis
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Paronychia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Pneumonia
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.5%
7/40 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.7%
19/74 • Number of events 32 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Injury, poisoning and procedural complications
Tooth injury
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Alanine aminotransferase increased
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.4%
4/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.8%
8/74 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
20.0%
8/40 • Number of events 12 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Amylase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 14 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Aspartate aminotransferase increased
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
21.7%
5/23 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.2%
9/74 • Number of events 19 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
22.5%
9/40 • Number of events 14 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Blood and lymphatic system disorders
Anaemia
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.4%
4/23 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
23.0%
17/74 • Number of events 29 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
37.5%
3/8 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
30.0%
12/40 • Number of events 19 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Cardiac disorders
Sinus tachycardia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Dry eye
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
16.2%
12/74 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Glaucoma
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Retinal detachment
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Retinopathy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Growth of eyelashes
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Detachment of retinal pigment epithelium
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Eye disorders
Pingueculitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
14.9%
11/74 • Number of events 14 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Ascites
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Breath odour
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Constipation
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
43.5%
10/23 • Number of events 16 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
33.8%
25/74 • Number of events 41 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
37.5%
3/8 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.5%
7/40 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Diarrhoea
|
17.4%
4/23 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
56.5%
13/23 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
64.9%
48/74 • Number of events 106 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
50.0%
4/8 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
57.5%
23/40 • Number of events 42 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
33.8%
25/74 • Number of events 42 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
22.5%
9/40 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
37.5%
3/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Nausea
|
30.4%
7/23 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
34.8%
8/23 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
27.0%
20/74 • Number of events 31 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
50.0%
4/8 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
27.5%
11/40 • Number of events 19 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
16.2%
12/74 • Number of events 24 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
15.0%
6/40 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
C-reactive protein increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Gamma-glutamyltransferase increased
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 16 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Lipase increased
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.5%
10/74 • Number of events 40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
10/40 • Number of events 25 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Lymphocyte count decreased
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Neutrophil count decreased
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Platelet count decreased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Weight decreased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood phosphorus increased
|
47.8%
11/23 • Number of events 21 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
87.0%
20/23 • Number of events 58 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
41.9%
31/74 • Number of events 88 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
62.5%
5/8 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
77.5%
31/40 • Number of events 85 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 12 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
21.7%
5/23 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
20.0%
8/40 • Number of events 18 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 11 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 25 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 12 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.7%
5/23 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
43.5%
10/23 • Number of events 12 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
39.2%
29/74 • Number of events 50 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
50.0%
4/8 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
40.0%
16/40 • Number of events 18 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Metabolism and nutrition disorders
Hyperlipasaemia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
21.7%
5/23 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
23.0%
17/74 • Number of events 30 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
5/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.4%
4/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
16.2%
12/74 • Number of events 17 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.8%
8/74 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Musculoskeletal and connective tissue disorders
Chest wall haematoma
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Dizziness
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.5%
7/40 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Dysgeusia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
23.0%
17/74 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.5%
7/40 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Headache
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.7%
2/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Paraesthesia
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Syncope
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Nervous system disorders
Taste disorder
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Psychiatric disorders
Depression
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Psychiatric disorders
Insomnia
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
21.7%
5/23 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.2%
9/74 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.4%
4/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
32.5%
13/40 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.1%
3/74 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.0%
3/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.1%
6/74 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
30.0%
12/40 • Number of events 20 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
17.5%
7/40 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
8.7%
2/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
13.0%
3/23 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
26.1%
6/23 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
27.0%
20/74 • Number of events 23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
20.0%
8/40 • Number of events 10 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
23.0%
17/74 • Number of events 22 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Hypertrichosis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 13 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Nail dystrophy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 7 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Nail hypertrophy
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Onycholysis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
16.2%
12/74 • Number of events 22 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
8.7%
2/23 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
9.5%
7/74 • Number of events 16 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.7%
2/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
6.8%
5/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
10.0%
4/40 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 5 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 4 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
7.5%
3/40 • Number of events 9 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Surgical and medical procedures
Haemorrhoid operation
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
12.5%
1/8 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/40 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Hypertension
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.4%
4/74 • Number of events 6 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Vascular disorders
Hypotension
|
4.3%
1/23 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
4.3%
1/23 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
1.4%
1/74 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
25.0%
2/8 • Number of events 2 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
2.5%
1/40 • Number of events 1 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/23 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/74 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
0.00%
0/8 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
5.0%
2/40 • Number of events 3 • From the first study drug administration up to 30 days after the end of treatment with study drug.
The safety data were reported in groups as pre-specified in the Statistical Analysis Plan, and participants in the Dose Escalation phase were combined.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60