Trial Outcomes & Findings for Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma (NCT NCT01594125)
NCT ID: NCT01594125
Last Updated: 2016-02-12
Results Overview
The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase \[ALP\] elevation \>5x ULN, or total bilirubin \>3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP \> baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
up to 28 days
Results posted on
2016-02-12
Participant Flow
Participant milestones
| Measure |
Group I: Nintedanib 150mg Bid
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
12
|
3
|
4
|
7
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
12
|
3
|
4
|
7
|
Reasons for withdrawal
| Measure |
Group I: Nintedanib 150mg Bid
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
1
|
0
|
|
Overall Study
Progressive Disease
|
3
|
12
|
3
|
3
|
7
|
Baseline Characteristics
Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
Group I: Nintedanib 150mg Bid
n=4 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
67.0 years
STANDARD_DEVIATION 14.72 • n=5 Participants
|
63.1 years
STANDARD_DEVIATION 9.84 • n=7 Participants
|
73.3 years
STANDARD_DEVIATION 2.31 • n=5 Participants
|
66.5 years
STANDARD_DEVIATION 6.56 • n=4 Participants
|
67.4 years
STANDARD_DEVIATION 4.35 • n=21 Participants
|
66.1 years
STANDARD_DEVIATION 8.81 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
21 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: up to 28 daysPopulation: Patients from the MTD set: The MTD set contains only treated patients from the dose escalation that were not replaced for MTD determination.
The MTD is based on the incidence of Dose Limiting Toxicities (DLTs). A drug-related AE was considered as a DLT if one of the following met: CTCAE grade 4 thrombocytopenia of any duration, CTCAE grade 4 neutropenia lasting for ≥8 days, CTCAE grade 4 febrile neutropenia of any duration, CTCAE grade 3 or 4 non-haematologic toxicity (with the following exception: Alopecia, Vomiting, nausea, or diarrhoea with no adequate supportive care, Transient electrolyte abnormality, which resolves spontaneously or can be corrected with appropriate treatment within 3 days, Liver toxicity), Liver enzyme toxicity of AST, ALT, alkaline phosphatase \[ALP\] elevation \>5x ULN, or total bilirubin \>3x ULN if baseline liver enzymes are within the normal range, or AST, ALT or ALP \> baseline value + 4x ULN if the baseline value is elevated. The MTD was determined to be 200mg bid.
Outcome measures
| Measure |
Group I: Nintedanib 150mg Bid
n=3 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=3 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: up to 28 monthsPopulation: Treated Set (TS): The treated set includes all patients who were administered at least one dose of any study medication.
Objective response (Complete response (CR) + Partial response (PR), regardless of confirmation) is derived from a patient's best objective response by RECIST. Best objective response is calculated based on the "overall" visit response from each assessment. Best objective response represents the best response a patient has had during their time in the study up until progression, last evaluable assessment in the absence of progression or the start of subsequent anti-cancer therapy. For patients whose progression event is death, best objective response will be calculated based on data up until the last evaluable RECIST assessment prior to death.
Outcome measures
| Measure |
Group I: Nintedanib 150mg Bid
n=4 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: up to 28 monthsPopulation: Patients from TS
PFS is defined as the duration from start date of the study treatment to PD according to RECIST 1.0, or any death whichever occurs earlier.
Outcome measures
| Measure |
Group I: Nintedanib 150mg Bid
n=4 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Progression Free Survival (PFS)
|
6.05 months
Interval 0.95 to 8.25
|
2.76 months
Interval 1.74 to 5.42
|
7.26 months
Interval 3.68 to 7.39
|
2.40 months
Interval 1.48 to 6.88
|
2.76 months
Interval 0.95 to 5.62
|
SECONDARY outcome
Timeframe: up to 28 monthsPopulation: Patients from TS
TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.
Outcome measures
| Measure |
Group I: Nintedanib 150mg Bid
n=4 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Time to Progression (TTP)
|
6.05 months
Interval 0.95 to 8.25
|
2.76 months
Interval 1.74 to 5.42
|
7.26 months
Interval 3.68 to 7.39
|
2.40 months
Interval 1.48 to 6.88
|
2.76 months
Interval 0.95 to 5.62
|
SECONDARY outcome
Timeframe: up to 28 monthsPopulation: Patients from TS and AFP evaluation (\>20μg/L) at baseline and post-baseline AFP assessment after two or three courses.
Response by AFP is defined as 20% or more decline in AFP between the baseline value and the AFP value after three courses (12 weeks) of therapy. If patients only receive two courses of therapy the AFP value after two courses (8 weeks) will be used for the analysis.
Outcome measures
| Measure |
Group I: Nintedanib 150mg Bid
n=3 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=6 Participants
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=2 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=4 Participants
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Number of Participants With Response by Alpha Fetoprotein (AFP)
|
2 participants
|
1 participants
|
1 participants
|
1 participants
|
1 participants
|
Adverse Events
Group I: Nintedanib 150mg Bid
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group I: Nintedanib 200mg Bid
Serious events: 4 serious events
Other events: 12 other events
Deaths: 0 deaths
Group II: Nintedanib 100mg Bid
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Group II: Nintedanib 150mg Bid
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Group II: Nintedanib 200mg Bid
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group I: Nintedanib 150mg Bid
n=4 participants at risk
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 participants at risk
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Immune thrombocytopenic purpura
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Pyrexia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
50.0%
2/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour embolism
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
Other adverse events
| Measure |
Group I: Nintedanib 150mg Bid
n=4 participants at risk
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 150mg twice daily
|
Group I: Nintedanib 200mg Bid
n=12 participants at risk
Patients with mild liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\<=2 x upper limit of normal (ULN)) and Child-Pugh A treated with Nintedanib 200mg twice daily
|
Group II: Nintedanib 100mg Bid
n=3 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 100mg twice daily
|
Group II: Nintedanib 150mg Bid
n=4 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 x to \<=5 upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 150mg twice daily
|
Group II: Nintedanib 200mg Bid
n=7 participants at risk
Patients with moderate liver dysfunction according to their aspartate amino transferase (AST)/ alanine amino transferase (ALT) values (\>2 to \<=5 x upper limit of normal (ULN)) and Child-Pugh B (score 7) treated with Nintedanib 200mg twice daily
|
|---|---|---|---|---|---|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Renal and urinary disorders
Ketonuria
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Renal and urinary disorders
Proteinuria
|
50.0%
2/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
42.9%
3/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
50.0%
2/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • up to 67 days
|
25.0%
3/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
50.0%
2/4 • up to 67 days
|
42.9%
3/7 • up to 67 days
|
|
Gastrointestinal disorders
Cheilitis
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • up to 67 days
|
58.3%
7/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
57.1%
4/7 • up to 67 days
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Enterocolitis
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Gastritis
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Loose tooth
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • up to 67 days
|
58.3%
7/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
100.0%
4/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • up to 67 days
|
50.0%
6/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
75.0%
3/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Chest discomfort
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Chest pain
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Fatigue
|
50.0%
2/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
75.0%
3/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Influenza like illness
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Localised oedema
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
General disorders
Malaise
|
0.00%
0/4 • up to 67 days
|
33.3%
4/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
General disorders
Oedema
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
General disorders
Oedema peripheral
|
25.0%
1/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
General disorders
Pyrexia
|
25.0%
1/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Infections and infestations
Bronchitis
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Infections and infestations
Cystitis
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Infections and infestations
Gingivitis
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
1/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Injury, poisoning and procedural complications
Wound complication
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Alanine aminotransferase increased
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Amylase increased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
1/4 • up to 67 days
|
25.0%
3/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
50.0%
2/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Blood alkaline phosphatase increased
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
75.0%
3/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Blood creatinine increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Investigations
Blood urea increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Blood uric acid increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
C-reactive protein increased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Eosinophil count increased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
Platelet count decreased
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Investigations
White blood cell count decreased
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
2/4 • up to 67 days
|
33.3%
4/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
100.0%
4/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
50.0%
2/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
66.7%
2/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4 • up to 67 days
|
25.0%
3/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Nervous system disorders
Dysgeusia
|
25.0%
1/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Nervous system disorders
Parosmia
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
25.0%
1/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
14.3%
1/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Skin and subcutaneous tissue disorders
Skin erosion
|
0.00%
0/4 • up to 67 days
|
0.00%
0/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
25.0%
1/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/4 • up to 67 days
|
16.7%
2/12 • up to 67 days
|
33.3%
1/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
28.6%
2/7 • up to 67 days
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/4 • up to 67 days
|
8.3%
1/12 • up to 67 days
|
0.00%
0/3 • up to 67 days
|
0.00%
0/4 • up to 67 days
|
0.00%
0/7 • up to 67 days
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER