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Dose Escalation Study of Nintedanib (BIBF 1120) in Japanese Patients With Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT01594125
Recruitment Status : Completed
First Posted : May 8, 2012
Results First Posted : December 22, 2015
Last Update Posted : February 12, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Interventions Drug: Nintedanib high dose
Drug: Nintedanib low dose
Drug: Nintedanib medium dose
Enrollment 30

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description 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 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 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 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 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
Period Title: Overall Study
Started 4 12 3 4 7
Completed 0 0 0 0 0
Not Completed 4 12 3 4 7
Reason Not Completed
Withdrawal by Subject             1             0             0             1             0
Progressive Disease             3             12             3             3             7
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid Total
Hide Arm/Group Description 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 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 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 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 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 of all reporting groups
Overall Number of Baseline Participants 4 12 3 4 7 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 12 participants 3 participants 4 participants 7 participants 30 participants
67.0  (14.72) 63.1  (9.84) 73.3  (2.31) 66.5  (6.56) 67.4  (4.35) 66.1  (8.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 12 participants 3 participants 4 participants 7 participants 30 participants
Female
2
  50.0%
1
   8.3%
3
 100.0%
2
  50.0%
1
  14.3%
9
  30.0%
Male
2
  50.0%
11
  91.7%
0
   0.0%
2
  50.0%
6
  85.7%
21
  70.0%
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Nintedanib
Hide Description 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.
Time Frame up to 28 days
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Hide Analysis Population Description
Patients from the MTD set: The MTD set contains only treated patients from the dose escalation that were not replaced for MTD determination.
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description:
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
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
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
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
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 Number of Participants Analyzed 3 3 3 3 3
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0
2.Secondary Outcome
Title Number of Participants With Objective Tumour Response According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Hide Description 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.
Time Frame up to 28 months
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Hide Analysis Population Description
Treated Set (TS): The treated set includes all patients who were administered at least one dose of any study medication.
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description:
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
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
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
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
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 Number of Participants Analyzed 4 12 3 4 7
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame up to 28 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients from TS
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description:
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
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
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
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
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 Number of Participants Analyzed 4 12 3 4 7
Median (Inter-Quartile Range)
Unit of Measure: months
6.05
(0.95 to 8.25)
2.76
(1.74 to 5.42)
7.26
(3.68 to 7.39)
2.40
(1.48 to 6.88)
2.76
(0.95 to 5.62)
4.Secondary Outcome
Title Time to Progression (TTP)
Hide Description TTP is defined as the duration from the start date of the study treatment to PD according to RECIST 1.0.
Time Frame up to 28 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients from TS
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description:
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
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
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
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
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 Number of Participants Analyzed 4 12 3 4 7
Median (Inter-Quartile Range)
Unit of Measure: months
6.05
(0.95 to 8.25)
2.76
(1.74 to 5.42)
7.26
(3.68 to 7.39)
2.40
(1.48 to 6.88)
2.76
(0.95 to 5.62)
5.Secondary Outcome
Title Number of Participants With Response by Alpha Fetoprotein (AFP)
Hide Description 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.
Time Frame up to 28 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients from TS and AFP evaluation (>20μg/L) at baseline and post-baseline AFP assessment after two or three courses.
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description:
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
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
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
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
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 Number of Participants Analyzed 3 6 3 2 4
Measure Type: Number
Unit of Measure: participants
2 1 1 1 1
Time Frame up to 67 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Hide Arm/Group Description 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 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 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 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 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
All-Cause Mortality
Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   4/12 (33.33%)   1/3 (33.33%)   2/4 (50.00%)   3/7 (42.86%) 
Blood and lymphatic system disorders           
Immune thrombocytopenic purpura  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Ascites  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
General disorders           
Pyrexia  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Hepatobiliary disorders           
Drug-induced liver injury  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Infections and infestations           
Gastroenteritis  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Metabolism and nutrition disorders           
Hyponatraemia  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Malignant neoplasm progression  1  0/4 (0.00%)  1/12 (8.33%)  1/3 (33.33%)  2/4 (50.00%)  1/7 (14.29%) 
Tumour embolism  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group I: Nintedanib 150mg Bid Group I: Nintedanib 200mg Bid Group II: Nintedanib 100mg Bid Group II: Nintedanib 150mg Bid Group II: Nintedanib 200mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   12/12 (100.00%)   3/3 (100.00%)   4/4 (100.00%)   7/7 (100.00%) 
Blood and lymphatic system disorders           
Leukopenia  1  0/4 (0.00%)  0/12 (0.00%)  2/3 (66.67%)  0/4 (0.00%)  1/7 (14.29%) 
Lymphopenia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  1/7 (14.29%) 
Neutropenia  1  2/4 (50.00%)  0/12 (0.00%)  2/3 (66.67%)  1/4 (25.00%)  0/7 (0.00%) 
Thrombocytopenia  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Gastrointestinal disorders           
Abdominal discomfort  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Abdominal distension  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Abdominal pain  1  0/4 (0.00%)  3/12 (25.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Abdominal pain upper  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/7 (0.00%) 
Ascites  1  0/4 (0.00%)  1/12 (8.33%)  1/3 (33.33%)  2/4 (50.00%)  3/7 (42.86%) 
Cheilitis  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Constipation  1  0/4 (0.00%)  2/12 (16.67%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Diarrhoea  1  1/4 (25.00%)  7/12 (58.33%)  1/3 (33.33%)  1/4 (25.00%)  4/7 (57.14%) 
Dry mouth  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Enterocolitis  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Flatulence  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Gastritis  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Gingival bleeding  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Haemorrhoids  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Loose tooth  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Nausea  1  0/4 (0.00%)  7/12 (58.33%)  0/3 (0.00%)  4/4 (100.00%)  1/7 (14.29%) 
Stomatitis  1  0/4 (0.00%)  2/12 (16.67%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Vomiting  1  0/4 (0.00%)  6/12 (50.00%)  0/3 (0.00%)  3/4 (75.00%)  0/7 (0.00%) 
General disorders           
Chest discomfort  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Chest pain  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Fatigue  1  2/4 (50.00%)  1/12 (8.33%)  2/3 (66.67%)  3/4 (75.00%)  0/7 (0.00%) 
Influenza like illness  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Localised oedema  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Malaise  1  0/4 (0.00%)  4/12 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  2/7 (28.57%) 
Oedema  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Oedema peripheral  1  1/4 (25.00%)  1/12 (8.33%)  1/3 (33.33%)  1/4 (25.00%)  1/7 (14.29%) 
Pyrexia  1  1/4 (25.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  2/7 (28.57%) 
Hepatobiliary disorders           
Drug-induced liver injury  1  0/4 (0.00%)  2/12 (16.67%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Hyperbilirubinaemia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Infections and infestations           
Bronchitis  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Cystitis  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Gingivitis  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Nasopharyngitis  1  1/4 (25.00%)  2/12 (16.67%)  1/3 (33.33%)  0/4 (0.00%)  1/7 (14.29%) 
Pneumonia  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Injury, poisoning and procedural complications           
Radiation oesophagitis  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Rib fracture  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Soft tissue injury  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Wound complication  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  1/4 (25.00%)  0/12 (0.00%)  2/3 (66.67%)  1/4 (25.00%)  1/7 (14.29%) 
Amylase increased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Aspartate aminotransferase increased  1  1/4 (25.00%)  3/12 (25.00%)  2/3 (66.67%)  2/4 (50.00%)  1/7 (14.29%) 
Blood alkaline phosphatase increased  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Blood bilirubin increased  1  0/4 (0.00%)  1/12 (8.33%)  1/3 (33.33%)  3/4 (75.00%)  0/7 (0.00%) 
Blood creatine phosphokinase increased  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/7 (0.00%) 
Blood creatinine increased  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Blood lactate dehydrogenase increased  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Blood thyroid stimulating hormone increased  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  2/7 (28.57%) 
Blood urea increased  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Blood uric acid increased  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
C-reactive protein increased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Electrocardiogram QT prolonged  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Eosinophil count increased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Gamma-glutamyltransferase increased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  1/7 (14.29%) 
Haemoglobin decreased  1  0/4 (0.00%)  1/12 (8.33%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Hepatic enzyme increased  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Neutrophil count decreased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Platelet count decreased  1  0/4 (0.00%)  2/12 (16.67%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
White blood cell count decreased  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  2/4 (50.00%)  4/12 (33.33%)  1/3 (33.33%)  4/4 (100.00%)  2/7 (28.57%) 
Dehydration  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Hyperglycaemia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Hyperuricaemia  1  0/4 (0.00%)  1/12 (8.33%)  1/3 (33.33%)  0/4 (0.00%)  2/7 (28.57%) 
Hypoalbuminaemia  1  0/4 (0.00%)  2/12 (16.67%)  2/3 (66.67%)  2/4 (50.00%)  2/7 (28.57%) 
Hypokalaemia  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Hyponatraemia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Hypophosphataemia  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/4 (0.00%)  0/12 (0.00%)  2/3 (66.67%)  0/4 (0.00%)  0/7 (0.00%) 
Back pain  1  0/4 (0.00%)  3/12 (25.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Muscle spasms  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Tumour pain  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/7 (14.29%) 
Nervous system disorders           
Dysgeusia  1  1/4 (25.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Headache  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/7 (14.29%) 
Hypoaesthesia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Neuropathy peripheral  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Parosmia  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Somnolence  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Psychiatric disorders           
Insomnia  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Psychotic disorder  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Renal and urinary disorders           
Chromaturia  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Ketonuria  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Proteinuria  1  2/4 (50.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  3/7 (42.86%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory distress syndrome  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Cough  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Dysphonia  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Dyspnoea  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Epistaxis  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Hypoxia  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Pleural effusion  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Pulmonary haemorrhage  1  0/4 (0.00%)  0/12 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/7 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Dry skin  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/4 (25.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Pruritus  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/7 (14.29%) 
Rash  1  0/4 (0.00%)  2/12 (16.67%)  1/3 (33.33%)  0/4 (0.00%)  1/7 (14.29%) 
Rash maculo-papular  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Skin erosion  1  0/4 (0.00%)  0/12 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/7 (0.00%) 
Vascular disorders           
Hypertension  1  0/4 (0.00%)  2/12 (16.67%)  1/3 (33.33%)  0/4 (0.00%)  2/7 (28.57%) 
Orthostatic hypotension  1  0/4 (0.00%)  1/12 (8.33%)  0/3 (0.00%)  0/4 (0.00%)  0/7 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01594125     History of Changes
Other Study ID Numbers: 1199.120
First Submitted: May 2, 2012
First Posted: May 8, 2012
Results First Submitted: November 17, 2015
Results First Posted: December 22, 2015
Last Update Posted: February 12, 2016