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INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis. (JUMP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01493414
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myelofibrosis
Intervention Drug: INC424
Enrollment 2233
Recruitment Details This was an expanded access study intended to provide an access path to ruxolitinib for patients with Myelofibrosis (MF) and to allow for collection of additional safety and efficacy data for ruxolitinib.
Pre-assignment Details  
Arm/Group Title INC424
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5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Period Title: Overall Study
Started 2233
Completed 1283
Not Completed 950
Reason Not Completed
Adverse Event             405
Disease progression             204
Death             101
Physician Decision             93
Withdrawal by Subject             79
Protocol deviation             27
Administrative problems             25
Lost to Follow-up             16
Arm/Group Title INC424
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5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Baseline Participants 2233
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2233 participants
65.6  (10.50)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2233 participants
Female
1016
  45.5%
Male
1217
  54.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2233 participants
American Indian or Alaska Native
6
   0.3%
Asian
23
   1.0%
Native Hawaiian or Other Pacific Islander
1
   0.0%
Black or African American
20
   0.9%
White
2087
  93.5%
More than one race
96
   4.3%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2233 participants
Hispanic/Latino
509
  22.8%
Chinese
1
   0.0%
Indian (Indian subcontinent)
1
   0.0%
Japanese
0
   0.0%
Mixed Ethnicity
15
   0.7%
Others
1707
  76.4%
ECOG score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2233 participants
0
1061
  47.5%
1
960
  43.0%
2
197
   8.8%
3
1
   0.0%
4
0
   0.0%
Missing
14
   0.6%
[1]
Measure Description: ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years
Hide Description An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.
Time Frame Baseline up to approximately 5 years
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Hide Analysis Population Description
Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Arm/Group Title INC424
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5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2233
Measure Type: Count of Participants
Unit of Measure: Participants
Adverse Events
2153
  96.4%
Serious adverse events
830
  37.2%
2.Secondary Outcome
Title Percentage of Participants With at Least 50% Reduction in Spleen Length
Hide Description Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).
Time Frame Baseline up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug.
Arm/Group Title INC424
Hide Arm/Group Description:

5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2049
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
71.7
(69.7 to 73.7)
3.Secondary Outcome
Title Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length
Hide Description

Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.

Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length.

Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length.

Time Frame Baseline up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug and were observed from baseline in to the study follow-up period.
Arm/Group Title INC424 - Responders INC424 - Stable Disease INC424 - Progressive Disease INC424 - Missing
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Responders with spleen length between 5 and 10 cm=non palpable spleen. Responders with spleen length more than 10 cm=Spleen reduction of 50% from baseline.

5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression.

Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression.

5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length.

Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length.

5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Missing values.

5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2178 2178 2178 2178
Measure Type: Count of Participants
Unit of Measure: Participants
Spleen length at baseline-Less than 5 cm Number Analyzed 189 participants 189 participants 189 participants 189 participants
NA [1]  NA [1]  NA [1]  NA [1] 
Spleen length at baseline-Between 5 and 10 cm Number Analyzed 765 participants 765 participants 765 participants 765 participants
421
  55.0%
334
  43.7%
1
   0.1%
9
   1.2%
Spleen length at baseline-More than 10 cm Number Analyzed 1224 participants 1224 participants 1224 participants 1224 participants
742
  60.6%
463
  37.8%
0
   0.0%
19
   1.6%
[1]
Patients with spleen length less than 5 cm are not evaluable (NE) for response.
4.Secondary Outcome
Title Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years
Hide Description ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.
Time Frame Baseline up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug.
Arm/Group Title INC424
Hide Arm/Group Description:

5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2233
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline - Grade 0 Number Analyzed 1061 participants
Worst value post-baseline: Grade 0
598
  56.4%
Worst value post-baseline: Grade 1
377
  35.5%
Worst value post-baseline: Grade 2
62
   5.8%
Worst value post-baseline: Grade 3
12
   1.1%
Worst value post-baseline: Grade 4
7
   0.7%
Worst value post-baseline: Grade 5
0
   0.0%
Worst value post-baseline: Missing
5
   0.5%
Baseline - Grade 1 Number Analyzed 960 participants
Worst value post-baseline: Grade 0
89
   9.3%
Worst value post-baseline: Grade 1
629
  65.5%
Worst value post-baseline: Grade 2
187
  19.5%
Worst value post-baseline: Grade 3
26
   2.7%
Worst value post-baseline: Grade 4
12
   1.3%
Worst value post-baseline: Grade 5
1
   0.1%
Worst value post-baseline: Missing
16
   1.7%
Baseline - Grade 2 Number Analyzed 197 participants
Worst value post-baseline: Grade 0
3
   1.5%
Worst value post-baseline: Grade 1
43
  21.8%
Worst value post-baseline: Grade 2
111
  56.3%
Worst value post-baseline: Grade 3
20
  10.2%
Worst value post-baseline: Grade 4
12
   6.1%
Worst value post-baseline: Grade 5
1
   0.5%
Worst value post-baseline: Missing
7
   3.6%
Baseline - Grade 3 Number Analyzed 1 participants
Worst value post-baseline: Grade 0
0
   0.0%
Worst value post-baseline: Grade 1
0
   0.0%
Worst value post-baseline: Grade 2
0
   0.0%
Worst value post-baseline: Grade 3
1
 100.0%
Worst value post-baseline: Grade 4
0
   0.0%
Worst value post-baseline: Grade 5
0
   0.0%
Worst value post-baseline: Missing
0
   0.0%
Baseline - Grade 4 Number Analyzed 0 participants
Worst value post-baseline: Grade 0 0
Worst value post-baseline: Grade 1 0
Worst value post-baseline: Grade 2 0
Worst value post-baseline: Grade 3 0
Worst value post-baseline: Grade 4 0
Worst value post-baseline: Grade 5 0
Worst value post-baseline: Missing 0
Baseline - Missing Number Analyzed 14 participants
Worst value post-baseline: Grade 0
1
   7.1%
Worst value post-baseline: Grade 1
8
  57.1%
Worst value post-baseline: Grade 2
4
  28.6%
Worst value post-baseline: Grade 3
1
   7.1%
Worst value post-baseline: Grade 4
0
   0.0%
Worst value post-baseline: Grade 5
0
   0.0%
Worst value post-baseline: Missing
0
   0.0%
5.Secondary Outcome
Title Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48
Hide Description The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL.
Time Frame Baseline and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug.
Arm/Group Title INC424
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5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2233
Mean (Standard Deviation)
Unit of Measure: scores on a scale
FACT-Lymphoma Baseline Number Analyzed 2065 participants
42.3  (10.20)
FACT-Lymphoma Week 48 Number Analyzed 952 participants
47.9  (8.47)
FACT-Lymphoma TOI Baseline Number Analyzed 2034 participants
77.9  (18.99)
FACT-Lymphoma TOI Week 48 Number Analyzed 940 participants
86.8  (16.42)
FACT-Lymphoma total score Baseline Number Analyzed 2029 participants
113.9  (24.01)
FACT-Lymphoma total score Week 48 Number Analyzed 937 participants
123.3  (22.34)
FACT-G Baseline Number Analyzed 2050 participants
71.6  (15.98)
FACT-G Week 48 Number Analyzed 950 participants
75.5  (15.59)
6.Secondary Outcome
Title Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status
Hide Description Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration.
Time Frame Baseline up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug.
Arm/Group Title INC424
Hide Arm/Group Description:

5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2233
Median (95% Confidence Interval)
Unit of Measure: weeks
FACT-Lym Total score median time to improvement
10.9
(5.1 to 11.6)
FACIT – Fatigue score median time to improvement
4.6
(4.4 to 4.6)
ECOG score median time to improvement
63.1
(61.1 to 65.0)
7.Secondary Outcome
Title Medical Resource Utilization up to 5 Years
Hide Description Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.
Time Frame Baseline up to approximately 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set includes all patients who received at least one administration of study drug.
Arm/Group Title INC424
Hide Arm/Group Description:

5 - 25 mg twice a day (BID)

INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Overall Number of Participants Analyzed 2233
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline- Dependency Number Analyzed 158 participants
End of Study - Dependency
129
  81.6%
End of Study - Independency
29
  18.4%
Baseline- Independency Number Analyzed 2075 participants
End of Study - Dependency
480
  23.1%
End of Study - Independency
1595
  76.9%
Time Frame Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years .
Adverse Event Reporting Description

Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.

 
Arm/Group Title INC424
Hide Arm/Group Description All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 25 mg twice a day. No INC424 dose will exceed 20 mg BID orally.
All-Cause Mortality
INC424
Affected / at Risk (%)
Total   205/2233 (9.18%) 
Show Serious Adverse Events Hide Serious Adverse Events
INC424
Affected / at Risk (%)
Total   830/2233 (37.17%) 
Blood and lymphatic system disorders   
Agranulocytosis  1  1/2233 (0.04%) 
Anaemia  1  94/2233 (4.21%) 
Autoimmune haemolytic anaemia  1  1/2233 (0.04%) 
Bone marrow oedema  1  1/2233 (0.04%) 
Coagulopathy  1  1/2233 (0.04%) 
Disseminated intravascular coagulation  1  1/2233 (0.04%) 
Febrile neutropenia  1  8/2233 (0.36%) 
Haemolytic anaemia  1  2/2233 (0.09%) 
Histiocytosis haematophagic  1  1/2233 (0.04%) 
Hypercoagulation  1  1/2233 (0.04%) 
Leukocytosis  1  8/2233 (0.36%) 
Leukostasis syndrome  1  1/2233 (0.04%) 
Lymphadenopathy  1  1/2233 (0.04%) 
Lymphocytosis  1  1/2233 (0.04%) 
Monoclonal B-cell lymphocytosis  1  1/2233 (0.04%) 
Neutropenia  1  10/2233 (0.45%) 
Pancytopenia  1  3/2233 (0.13%) 
Polycythaemia  1  1/2233 (0.04%) 
Splenic haematoma  1  3/2233 (0.13%) 
Splenic infarction  1  4/2233 (0.18%) 
Splenomegaly  1  8/2233 (0.36%) 
Spontaneous haematoma  1  1/2233 (0.04%) 
Thrombocytopenia  1  24/2233 (1.07%) 
Thrombocytosis  1  1/2233 (0.04%) 
Cardiac disorders   
Acute coronary syndrome  1  2/2233 (0.09%) 
Acute myocardial infarction  1  9/2233 (0.40%) 
Angina pectoris  1  8/2233 (0.36%) 
Aortic valve incompetence  1  1/2233 (0.04%) 
Atrial fibrillation  1  21/2233 (0.94%) 
Atrioventricular block  1  1/2233 (0.04%) 
Atrioventricular block first degree  1  1/2233 (0.04%) 
Bradycardia  1  4/2233 (0.18%) 
Cardiac arrest  1  16/2233 (0.72%) 
Cardiac disorder  1  3/2233 (0.13%) 
Cardiac failure  1  43/2233 (1.93%) 
Cardiac failure acute  1  5/2233 (0.22%) 
Cardiac failure chronic  1  1/2233 (0.04%) 
Cardiac failure congestive  1  7/2233 (0.31%) 
Cardiac tamponade  1  2/2233 (0.09%) 
Cardio-respiratory arrest  1  9/2233 (0.40%) 
Cardiogenic shock  1  5/2233 (0.22%) 
Cardiopulmonary failure  1  1/2233 (0.04%) 
Conduction disorder  1  1/2233 (0.04%) 
Congestive cardiomyopathy  1  1/2233 (0.04%) 
Cor pulmonale  1  1/2233 (0.04%) 
Coronary artery disease  1  5/2233 (0.22%) 
Coronary artery stenosis  1  1/2233 (0.04%) 
Hypertensive heart disease  1  1/2233 (0.04%) 
Intracardiac thrombus  1  1/2233 (0.04%) 
Left ventricular dysfunction  1  1/2233 (0.04%) 
Left ventricular failure  1  1/2233 (0.04%) 
Left ventricular hypertrophy  1  1/2233 (0.04%) 
Mitral valve incompetence  1  2/2233 (0.09%) 
Myocardial infarction  1  5/2233 (0.22%) 
Myocardial ischaemia  1  2/2233 (0.09%) 
Palpitations  1  1/2233 (0.04%) 
Pericardial effusion  1  3/2233 (0.13%) 
Pericardial haemorrhage  1  1/2233 (0.04%) 
Pericarditis  1  1/2233 (0.04%) 
Right ventricular dysfunction  1  1/2233 (0.04%) 
Right ventricular failure  1  2/2233 (0.09%) 
Sinus node dysfunction  1  1/2233 (0.04%) 
Sinus tachycardia  1  1/2233 (0.04%) 
Stress cardiomyopathy  1  2/2233 (0.09%) 
Supraventricular tachycardia  1  3/2233 (0.13%) 
Tachyarrhythmia  1  1/2233 (0.04%) 
Tachycardia  1  1/2233 (0.04%) 
Tricuspid valve incompetence  1  1/2233 (0.04%) 
Ventricular dysfunction  1  1/2233 (0.04%) 
Ventricular hypokinesia  1  1/2233 (0.04%) 
Congenital, familial and genetic disorders   
Hydrocele  1  2/2233 (0.09%) 
Ear and labyrinth disorders   
Hypoacusis  1  2/2233 (0.09%) 
Vertigo  1  5/2233 (0.22%) 
Endocrine disorders   
Adrenal insufficiency  1  1/2233 (0.04%) 
Eye disorders   
Cataract  1  3/2233 (0.13%) 
Corneal oedema  1  1/2233 (0.04%) 
Diplopia  1  1/2233 (0.04%) 
Macular degeneration  1  1/2233 (0.04%) 
Optic ischaemic neuropathy  1  1/2233 (0.04%) 
Uveitis  1  1/2233 (0.04%) 
Gastrointestinal disorders   
Abdominal hernia  1  1/2233 (0.04%) 
Abdominal mass  1  1/2233 (0.04%) 
Abdominal pain  1  28/2233 (1.25%) 
Abdominal pain lower  1  1/2233 (0.04%) 
Abdominal pain upper  1  5/2233 (0.22%) 
Abdominal tenderness  1  1/2233 (0.04%) 
Abdominal wall haematoma  1  1/2233 (0.04%) 
Anal fissure  1  2/2233 (0.09%) 
Anal prolapse  1  1/2233 (0.04%) 
Anal ulcer  1  1/2233 (0.04%) 
Ascites  1  14/2233 (0.63%) 
Barrett's oesophagus  1  1/2233 (0.04%) 
Colitis  1  3/2233 (0.13%) 
Constipation  1  2/2233 (0.09%) 
Diarrhoea  1  17/2233 (0.76%) 
Diarrhoea haemorrhagic  1  1/2233 (0.04%) 
Diverticular perforation  1  2/2233 (0.09%) 
Diverticulum intestinal haemorrhagic  1  1/2233 (0.04%) 
Enteritis  1  1/2233 (0.04%) 
Enterovesical fistula  1  1/2233 (0.04%) 
Faecaloma  1  1/2233 (0.04%) 
Femoral hernia  1  1/2233 (0.04%) 
Gastric haemorrhage  1  4/2233 (0.18%) 
Gastric stenosis  1  1/2233 (0.04%) 
Gastric ulcer  1  1/2233 (0.04%) 
Gastric varices haemorrhage  1  1/2233 (0.04%) 
Gastritis  1  1/2233 (0.04%) 
Gastrointestinal haemorrhage  1  21/2233 (0.94%) 
Haematemesis  1  2/2233 (0.09%) 
Haematochezia  1  2/2233 (0.09%) 
Haemorrhoids  1  1/2233 (0.04%) 
Ileus  1  1/2233 (0.04%) 
Ileus paralytic  1  3/2233 (0.13%) 
Inguinal hernia  1  5/2233 (0.22%) 
Inguinal hernia strangulated  1  1/2233 (0.04%) 
Intestinal haemorrhage  1  2/2233 (0.09%) 
Intestinal infarction  1  1/2233 (0.04%) 
Intestinal obstruction  1  2/2233 (0.09%) 
Intestinal perforation  1  1/2233 (0.04%) 
Mallory-Weiss syndrome  1  1/2233 (0.04%) 
Melaena  1  4/2233 (0.18%) 
Mesenteric haemorrhage  1  1/2233 (0.04%) 
Mesenteric vein thrombosis  1  2/2233 (0.09%) 
Mouth haemorrhage  1  1/2233 (0.04%) 
Nausea  1  5/2233 (0.22%) 
Oesophageal haemorrhage  1  2/2233 (0.09%) 
Oesophageal rupture  1  1/2233 (0.04%) 
Oesophageal varices haemorrhage  1  10/2233 (0.45%) 
Pancreatitis  1  2/2233 (0.09%) 
Peritoneal haemorrhage  1  2/2233 (0.09%) 
Pneumoperitoneum  1  1/2233 (0.04%) 
Rectal haemorrhage  1  3/2233 (0.13%) 
Rectal polyp  1  1/2233 (0.04%) 
Retroperitoneal haematoma  1  2/2233 (0.09%) 
Retroperitoneal haemorrhage  1  1/2233 (0.04%) 
Small intestinal obstruction  1  1/2233 (0.04%) 
Small intestinal stenosis  1  1/2233 (0.04%) 
Splenic artery aneurysm  1  1/2233 (0.04%) 
Subileus  1  3/2233 (0.13%) 
Tooth loss  1  1/2233 (0.04%) 
Toothache  1  1/2233 (0.04%) 
Upper gastrointestinal haemorrhage  1  5/2233 (0.22%) 
Varices oesophageal  1  5/2233 (0.22%) 
Vomiting  1  16/2233 (0.72%) 
General disorders   
Asthenia  1  14/2233 (0.63%) 
Chest pain  1  8/2233 (0.36%) 
Death  1  12/2233 (0.54%) 
Disease progression  1  4/2233 (0.18%) 
Drug withdrawal syndrome  1  2/2233 (0.09%) 
Face oedema  1  1/2233 (0.04%) 
Fatigue  1  11/2233 (0.49%) 
Gait disturbance  1  1/2233 (0.04%) 
General physical health deterioration  1  19/2233 (0.85%) 
Generalised oedema  1  5/2233 (0.22%) 
Hernia  1  1/2233 (0.04%) 
Hyperpyrexia  1  2/2233 (0.09%) 
Malaise  1  1/2233 (0.04%) 
Multiple organ dysfunction syndrome  1  11/2233 (0.49%) 
Nodule  1  1/2233 (0.04%) 
Non-cardiac chest pain  1  1/2233 (0.04%) 
Oedema peripheral  1  10/2233 (0.45%) 
Pain  1  1/2233 (0.04%) 
Peripheral swelling  1  1/2233 (0.04%) 
Polyp  1  1/2233 (0.04%) 
Pseudocyst  1  1/2233 (0.04%) 
Pyrexia  1  79/2233 (3.54%) 
Sudden death  1  2/2233 (0.09%) 
Hepatobiliary disorders   
Bile duct stone  1  2/2233 (0.09%) 
Biliary colic  1  1/2233 (0.04%) 
Cholangitis chronic  1  1/2233 (0.04%) 
Cholecystitis  1  3/2233 (0.13%) 
Cholecystitis acute  1  3/2233 (0.13%) 
Cholelithiasis  1  5/2233 (0.22%) 
Hepatic failure  1  1/2233 (0.04%) 
Hepatitis  1  1/2233 (0.04%) 
Hepatorenal syndrome  1  1/2233 (0.04%) 
Hepatotoxicity  1  1/2233 (0.04%) 
Hyperbilirubinaemia  1  1/2233 (0.04%) 
Jaundice  1  1/2233 (0.04%) 
Portal hypertension  1  3/2233 (0.13%) 
Portal vein thrombosis  1  5/2233 (0.22%) 
Immune system disorders   
Cytokine release syndrome  1  1/2233 (0.04%) 
Hypersensitivity  1  1/2233 (0.04%) 
Immunosuppression  1  1/2233 (0.04%) 
Infections and infestations   
Actinomycosis  1  1/2233 (0.04%) 
Anal abscess  1  1/2233 (0.04%) 
Appendicitis  1  5/2233 (0.22%) 
Arthritis bacterial  1  2/2233 (0.09%) 
Aspergillus infection  1  1/2233 (0.04%) 
Atypical pneumonia  1  1/2233 (0.04%) 
Bacterial infection  1  2/2233 (0.09%) 
Biliary sepsis  1  1/2233 (0.04%) 
Bone tuberculosis  1  1/2233 (0.04%) 
Bronchitis  1  9/2233 (0.40%) 
Bronchitis bacterial  1  1/2233 (0.04%) 
Bronchopulmonary aspergillosis  1  2/2233 (0.09%) 
Campylobacter infection  1  1/2233 (0.04%) 
Cellulitis  1  8/2233 (0.36%) 
Cerebral toxoplasmosis  1  1/2233 (0.04%) 
Community acquired infection  1  1/2233 (0.04%) 
Corneal abscess  1  1/2233 (0.04%) 
Cystitis  1  1/2233 (0.04%) 
Dengue fever  1  1/2233 (0.04%) 
Dermo-hypodermitis  1  1/2233 (0.04%) 
Device related infection  1  2/2233 (0.09%) 
Device related sepsis  1  1/2233 (0.04%) 
Diverticulitis  1  2/2233 (0.09%) 
Endocarditis  1  2/2233 (0.09%) 
Enterococcal infection  1  1/2233 (0.04%) 
Enterococcal sepsis  1  1/2233 (0.04%) 
Epididymitis  1  1/2233 (0.04%) 
Erysipelas  1  3/2233 (0.13%) 
Escherichia infection  1  2/2233 (0.09%) 
Escherichia sepsis  1  6/2233 (0.27%) 
Escherichia urinary tract infection  1  1/2233 (0.04%) 
Gangrene  1  2/2233 (0.09%) 
Gastroenteritis  1  11/2233 (0.49%) 
Gastroenteritis norovirus  1  1/2233 (0.04%) 
Gastroenteritis salmonella  1  1/2233 (0.04%) 
Gastroenteritis viral  1  2/2233 (0.09%) 
Gastrointestinal infection  1  3/2233 (0.13%) 
Genital herpes  1  1/2233 (0.04%) 
H1N1 influenza  1  1/2233 (0.04%) 
Hepatic echinococciasis  1  1/2233 (0.04%) 
Hepatitis B  1  1/2233 (0.04%) 
Hepatitis E  1  1/2233 (0.04%) 
Hepatitis infectious  1  1/2233 (0.04%) 
Herpes simplex  1  1/2233 (0.04%) 
Herpes simplex pneumonia  1  1/2233 (0.04%) 
Herpes zoster  1  5/2233 (0.22%) 
Herpes zoster infection neurological  1  1/2233 (0.04%) 
Infection  1  3/2233 (0.13%) 
Infectious pleural effusion  1  1/2233 (0.04%) 
Influenza  1  5/2233 (0.22%) 
Klebsiella infection  1  2/2233 (0.09%) 
Localised infection  1  1/2233 (0.04%) 
Lower respiratory tract infection  1  3/2233 (0.13%) 
Lung abscess  1  1/2233 (0.04%) 
Lung infection  1  11/2233 (0.49%) 
Lymph node tuberculosis  1  3/2233 (0.13%) 
Meningitis  1  1/2233 (0.04%) 
Mycobacterial infection  1  1/2233 (0.04%) 
Neurocryptococcosis  1  1/2233 (0.04%) 
Ophthalmic herpes zoster  1  1/2233 (0.04%) 
Oral candidiasis  1  2/2233 (0.09%) 
Pelvic inflammatory disease  1  1/2233 (0.04%) 
Perirectal abscess  1  1/2233 (0.04%) 
Peritoneal tuberculosis  1  2/2233 (0.09%) 
Peritonitis  1  4/2233 (0.18%) 
Peritonitis bacterial  1  2/2233 (0.09%) 
Pharyngitis  1  2/2233 (0.09%) 
Pneumococcal infection  1  1/2233 (0.04%) 
Pneumocystis jirovecii infection  1  1/2233 (0.04%) 
Pneumonia  1  123/2233 (5.51%) 
Pneumonia bacterial  1  2/2233 (0.09%) 
Pneumonia pneumococcal  1  1/2233 (0.04%) 
Pseudomonal sepsis  1  1/2233 (0.04%) 
Psoas abscess  1  1/2233 (0.04%) 
Pulmonary sepsis  1  2/2233 (0.09%) 
Pulmonary tuberculosis  1  2/2233 (0.09%) 
Pulpitis dental  1  1/2233 (0.04%) 
Pyelonephritis  1  1/2233 (0.04%) 
Q fever  1  1/2233 (0.04%) 
Respiratory syncytial virus infection  1  1/2233 (0.04%) 
Respiratory tract infection  1  19/2233 (0.85%) 
Sepsis  1  31/2233 (1.39%) 
Septic shock  1  21/2233 (0.94%) 
Sinusitis  1  2/2233 (0.09%) 
Skin infection  1  6/2233 (0.27%) 
Soft tissue infection  1  1/2233 (0.04%) 
Staphylococcal infection  1  3/2233 (0.13%) 
Staphylococcal sepsis  1  1/2233 (0.04%) 
Streptococcal sepsis  1  1/2233 (0.04%) 
Subcutaneous abscess  1  1/2233 (0.04%) 
Tooth abscess  1  1/2233 (0.04%) 
Tracheitis  1  1/2233 (0.04%) 
Tracheobronchitis  1  1/2233 (0.04%) 
Tuberculosis  1  5/2233 (0.22%) 
Tubo-ovarian abscess  1  1/2233 (0.04%) 
Upper respiratory tract infection  1  3/2233 (0.13%) 
Urinary tract infection  1  23/2233 (1.03%) 
Urinary tract infection bacterial  1  1/2233 (0.04%) 
Urosepsis  1  8/2233 (0.36%) 
Vestibular neuronitis  1  1/2233 (0.04%) 
Viral infection  1  1/2233 (0.04%) 
Injury, poisoning and procedural complications   
Anastomotic leak  1  1/2233 (0.04%) 
Ankle fracture  1  2/2233 (0.09%) 
Arterial injury  1  1/2233 (0.04%) 
Brain contusion  1  1/2233 (0.04%) 
Craniocerebral injury  1  1/2233 (0.04%) 
Crush injury  1  1/2233 (0.04%) 
Face injury  1  2/2233 (0.09%) 
Facial bones fracture  1  1/2233 (0.04%) 
Fall  1  6/2233 (0.27%) 
Femoral neck fracture  1  1/2233 (0.04%) 
Femur fracture  1  6/2233 (0.27%) 
Foot fracture  1  2/2233 (0.09%) 
Fractured sacrum  1  1/2233 (0.04%) 
Head injury  1  4/2233 (0.18%) 
Heart injury  1  1/2233 (0.04%) 
Hip fracture  1  1/2233 (0.04%) 
Humerus fracture  1  2/2233 (0.09%) 
Joint injury  1  1/2233 (0.04%) 
Limb injury  1  1/2233 (0.04%) 
Lower limb fracture  1  1/2233 (0.04%) 
Lumbar vertebral fracture  1  2/2233 (0.09%) 
Meniscus injury  1  2/2233 (0.09%) 
Overdose  1  1/2233 (0.04%) 
Patella fracture  1  1/2233 (0.04%) 
Post procedural haemorrhage  1  4/2233 (0.18%) 
Rib fracture  1  2/2233 (0.09%) 
Road traffic accident  1  1/2233 (0.04%) 
Spinal compression fracture  1  1/2233 (0.04%) 
Spinal fracture  1  2/2233 (0.09%) 
Splenic injury  1  1/2233 (0.04%) 
Splenic rupture  1  7/2233 (0.31%) 
Subarachnoid haemorrhage  1  1/2233 (0.04%) 
Subdural haemorrhage  1  1/2233 (0.04%) 
Tendon rupture  1  1/2233 (0.04%) 
Thoracic vertebral fracture  1  1/2233 (0.04%) 
Transfusion reaction  1  1/2233 (0.04%) 
Traumatic fracture  1  1/2233 (0.04%) 
Traumatic haemorrhage  1  1/2233 (0.04%) 
Upper limb fracture  1  1/2233 (0.04%) 
Wound dehiscence  1  1/2233 (0.04%) 
Investigations   
Blast cell count increased  1  3/2233 (0.13%) 
Blood alkaline phosphatase increased  1  1/2233 (0.04%) 
Blood lactate dehydrogenase increased  1  2/2233 (0.09%) 
Body temperature increased  1  1/2233 (0.04%) 
C-reactive protein increased  1  2/2233 (0.09%) 
Cardioactive drug level increased  1  1/2233 (0.04%) 
Ejection fraction decreased  1  1/2233 (0.04%) 
Electrocardiogram QT prolonged  1  1/2233 (0.04%) 
Electrocardiogram T wave abnormal  1  1/2233 (0.04%) 
Electrocardiogram T wave amplitude increased  1  1/2233 (0.04%) 
Epstein-Barr virus antigen positive  1  1/2233 (0.04%) 
Gamma-glutamyltransferase increased  1  1/2233 (0.04%) 
General physical condition abnormal  1  4/2233 (0.18%) 
Haemoglobin decreased  1  2/2233 (0.09%) 
Heart rate irregular  1  1/2233 (0.04%) 
Hepatic enzyme increased  1  1/2233 (0.04%) 
Lipase increased  1  1/2233 (0.04%) 
Myeloblast count increased  1  1/2233 (0.04%) 
Platelet count decreased  1  1/2233 (0.04%) 
Portal vein pressure increased  1  1/2233 (0.04%) 
Sensory level abnormal  1  1/2233 (0.04%) 
Transaminases increased  1  1/2233 (0.04%) 
Troponin I increased  1  1/2233 (0.04%) 
White blood cell count increased  1  1/2233 (0.04%) 
Metabolism and nutrition disorders   
Cachexia  1  3/2233 (0.13%) 
Decreased appetite  1  1/2233 (0.04%) 
Dehydration  1  8/2233 (0.36%) 
Diabetes mellitus  1  3/2233 (0.13%) 
Diabetic metabolic decompensation  1  1/2233 (0.04%) 
Electrolyte imbalance  1  1/2233 (0.04%) 
Fluid retention  1  1/2233 (0.04%) 
Gout  1  3/2233 (0.13%) 
Hypercalcaemia  1  1/2233 (0.04%) 
Hyperkalaemia  1  8/2233 (0.36%) 
Hyperlactacidaemia  1  1/2233 (0.04%) 
Hyperuricaemia  1  1/2233 (0.04%) 
Hypocalcaemia  1  2/2233 (0.09%) 
Hypoglycaemia  1  3/2233 (0.13%) 
Hypokalaemia  1  1/2233 (0.04%) 
Hyponatraemia  1  3/2233 (0.13%) 
Hypophosphataemia  1  1/2233 (0.04%) 
Hypovolaemia  1  1/2233 (0.04%) 
Metabolic acidosis  1  3/2233 (0.13%) 
Tumour lysis syndrome  1  4/2233 (0.18%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/2233 (0.09%) 
Arthritis  1  2/2233 (0.09%) 
Arthropathy  1  1/2233 (0.04%) 
Back pain  1  8/2233 (0.36%) 
Bone pain  1  11/2233 (0.49%) 
Chondrocalcinosis pyrophosphate  1  1/2233 (0.04%) 
Compartment syndrome  1  1/2233 (0.04%) 
Crystal arthropathy  1  1/2233 (0.04%) 
Flank pain  1  1/2233 (0.04%) 
Gouty arthritis  1  1/2233 (0.04%) 
Haemarthrosis  1  1/2233 (0.04%) 
Intervertebral disc protrusion  1  1/2233 (0.04%) 
Meniscal degeneration  1  1/2233 (0.04%) 
Muscle haemorrhage  1  1/2233 (0.04%) 
Muscle tightness  1  1/2233 (0.04%) 
Muscular weakness  1  2/2233 (0.09%) 
Musculoskeletal chest pain  1  1/2233 (0.04%) 
Musculoskeletal pain  1  1/2233 (0.04%) 
Myalgia  1  1/2233 (0.04%) 
Neck pain  1  2/2233 (0.09%) 
Osteoarthritis  1  1/2233 (0.04%) 
Osteolysis  1  2/2233 (0.09%) 
Osteonecrosis  1  1/2233 (0.04%) 
Osteoporotic fracture  1  1/2233 (0.04%) 
Pain in extremity  1  4/2233 (0.18%) 
Rotator cuff syndrome  1  1/2233 (0.04%) 
Soft tissue necrosis  1  1/2233 (0.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acrochordon  1  1/2233 (0.04%) 
Acute leukaemia  1  13/2233 (0.58%) 
Acute myeloid leukaemia  1  18/2233 (0.81%) 
Adenocarcinoma pancreas  1  1/2233 (0.04%) 
B-cell lymphoma  1  1/2233 (0.04%) 
Basal cell carcinoma  1  10/2233 (0.45%) 
Bladder transitional cell carcinoma  1  1/2233 (0.04%) 
Blast cell crisis  1  1/2233 (0.04%) 
Chloroma  1  1/2233 (0.04%) 
Cholangiocarcinoma  1  1/2233 (0.04%) 
Chronic lymphocytic leukaemia  1  2/2233 (0.09%) 
Chronic myeloid leukaemia  1  1/2233 (0.04%) 
Chronic myeloid leukaemia transformation  1  2/2233 (0.09%) 
Chronic myelomonocytic leukaemia  1  1/2233 (0.04%) 
Intestinal adenocarcinoma  1  1/2233 (0.04%) 
Leukaemia  1  7/2233 (0.31%) 
Lung neoplasm malignant  1  4/2233 (0.18%) 
Lymphangioma  1  1/2233 (0.04%) 
Malignant melanoma  1  1/2233 (0.04%) 
Metastases to liver  1  1/2233 (0.04%) 
Metastases to lung  1  1/2233 (0.04%) 
Monoclonal gammopathy  1  1/2233 (0.04%) 
Myelofibrosis  1  5/2233 (0.22%) 
Myeloid metaplasia  1  2/2233 (0.09%) 
Neoplasm  1  2/2233 (0.09%) 
Neoplasm skin  1  3/2233 (0.13%) 
Neuroendocrine carcinoma  1  1/2233 (0.04%) 
Neuroendocrine tumour  1  1/2233 (0.04%) 
Non-Hodgkin's lymphoma  1  2/2233 (0.09%) 
Pelvic neoplasm  1  1/2233 (0.04%) 
Prostate cancer  1  4/2233 (0.18%) 
Rectal adenocarcinoma  1  1/2233 (0.04%) 
Second primary malignancy  1  1/2233 (0.04%) 
Squamous cell carcinoma  1  9/2233 (0.40%) 
Squamous cell carcinoma of skin  1  6/2233 (0.27%) 
Squamous cell carcinoma of the vagina  1  1/2233 (0.04%) 
Transitional cell carcinoma  1  1/2233 (0.04%) 
Tumour thrombosis  1  1/2233 (0.04%) 
Uterine leiomyoma  1  1/2233 (0.04%) 
Nervous system disorders   
Basilar artery aneurysm  1  1/2233 (0.04%) 
Central nervous system haemorrhage  1  1/2233 (0.04%) 
Central nervous system lesion  1  1/2233 (0.04%) 
Cerebral haemorrhage  1  2/2233 (0.09%) 
Cerebral ischaemia  1  1/2233 (0.04%) 
Cerebrovascular accident  1  4/2233 (0.18%) 
Coma  1  1/2233 (0.04%) 
Cranial nerve paralysis  1  1/2233 (0.04%) 
Dizziness  1  5/2233 (0.22%) 
Drop attacks  1  1/2233 (0.04%) 
Dysarthria  1  1/2233 (0.04%) 
Embolic stroke  1  1/2233 (0.04%) 
Encephalopathy  1  1/2233 (0.04%) 
Extrapyramidal disorder  1  1/2233 (0.04%) 
Generalised tonic-clonic seizure  1  1/2233 (0.04%) 
Haemorrhagic stroke  1  2/2233 (0.09%) 
Headache  1  3/2233 (0.13%) 
Hepatic encephalopathy  1  1/2233 (0.04%) 
Hydrocephalus  1  1/2233 (0.04%) 
Hyperaesthesia  1  1/2233 (0.04%) 
Ischaemic stroke  1  1/2233 (0.04%) 
Loss of consciousness  1  1/2233 (0.04%) 
Muscle contractions involuntary  1  1/2233 (0.04%) 
Myoclonus  1  1/2233 (0.04%) 
Neuralgia  1  1/2233 (0.04%) 
Neurological decompensation  1  1/2233 (0.04%) 
Neuropathy peripheral  1  3/2233 (0.13%) 
Osmotic demyelination syndrome  1  1/2233 (0.04%) 
Paraesthesia  1  1/2233 (0.04%) 
Parkinson's disease  1  1/2233 (0.04%) 
Posterior reversible encephalopathy syndrome  1  1/2233 (0.04%) 
Presyncope  1  1/2233 (0.04%) 
Pyramidal tract syndrome  1  1/2233 (0.04%) 
Sciatica  1  1/2233 (0.04%) 
Seizure  1  3/2233 (0.13%) 
Somnolence  1  1/2233 (0.04%) 
Speech disorder  1  1/2233 (0.04%) 
Syncope  1  11/2233 (0.49%) 
Transient ischaemic attack  1  5/2233 (0.22%) 
Product Issues   
Device leakage  1  1/2233 (0.04%) 
Psychiatric disorders   
Anxiety  1  1/2233 (0.04%) 
Anxiety disorder  1  1/2233 (0.04%) 
Confusional state  1  3/2233 (0.13%) 
Delirium  1  1/2233 (0.04%) 
Depression  1  1/2233 (0.04%) 
Disorientation  1  2/2233 (0.09%) 
Renal and urinary disorders   
Acute kidney injury  1  19/2233 (0.85%) 
Acute prerenal failure  1  1/2233 (0.04%) 
Anuria  1  1/2233 (0.04%) 
Calculus bladder  1  2/2233 (0.09%) 
Chronic kidney disease  1  6/2233 (0.27%) 
Dysuria  1  1/2233 (0.04%) 
Haematuria  1  2/2233 (0.09%) 
Hydronephrosis  1  1/2233 (0.04%) 
Nephrolithiasis  1  6/2233 (0.27%) 
Nephropathy  1  1/2233 (0.04%) 
Nephrotic syndrome  1  1/2233 (0.04%) 
Renal colic  1  3/2233 (0.13%) 
Renal failure  1  12/2233 (0.54%) 
Renal impairment  1  2/2233 (0.09%) 
Renal infarct  1  1/2233 (0.04%) 
Tubulointerstitial nephritis  1  1/2233 (0.04%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia  1  1/2233 (0.04%) 
Cervical dysplasia  1  1/2233 (0.04%) 
Menometrorrhagia  1  1/2233 (0.04%) 
Ovarian cyst  1  1/2233 (0.04%) 
Postmenopausal haemorrhage  1  1/2233 (0.04%) 
Prostatitis  1  2/2233 (0.09%) 
Testicular pain  1  1/2233 (0.04%) 
Respiratory, thoracic and mediastinal disorders   
Acute pulmonary oedema  1  4/2233 (0.18%) 
Acute respiratory distress syndrome  1  7/2233 (0.31%) 
Acute respiratory failure  1  7/2233 (0.31%) 
Alveolitis  1  1/2233 (0.04%) 
Asthma  1  1/2233 (0.04%) 
Bronchospasm  1  3/2233 (0.13%) 
Chronic obstructive pulmonary disease  1  3/2233 (0.13%) 
Chronic respiratory failure  1  1/2233 (0.04%) 
Cough  1  6/2233 (0.27%) 
Dyspnoea  1  36/2233 (1.61%) 
Emphysema  1  1/2233 (0.04%) 
Epistaxis  1  10/2233 (0.45%) 
Haemoptysis  1  4/2233 (0.18%) 
Haemothorax  1  1/2233 (0.04%) 
Hydrothorax  1  1/2233 (0.04%) 
Interstitial lung disease  1  3/2233 (0.13%) 
Lung infiltration  1  2/2233 (0.09%) 
Oropharyngeal pain  1  1/2233 (0.04%) 
Pleural effusion  1  13/2233 (0.58%) 
Pneumonia aspiration  1  1/2233 (0.04%) 
Pneumonitis  1  5/2233 (0.22%) 
Pneumothorax  1  1/2233 (0.04%) 
Productive cough  1  1/2233 (0.04%) 
Pulmonary embolism  1  18/2233 (0.81%) 
Pulmonary haemorrhage  1  1/2233 (0.04%) 
Pulmonary hypertension  1  8/2233 (0.36%) 
Pulmonary oedema  1  5/2233 (0.22%) 
Respiratory distress  1  2/2233 (0.09%) 
Respiratory failure  1  26/2233 (1.16%) 
Thoracic haemorrhage  1  1/2233 (0.04%) 
Skin and subcutaneous tissue disorders   
Dermal cyst  1  1/2233 (0.04%) 
Dermatitis  1  1/2233 (0.04%) 
Erythema nodosum  1  1/2233 (0.04%) 
Hyperhidrosis  1  1/2233 (0.04%) 
Panniculitis  1  1/2233 (0.04%) 
Pruritus  1  2/2233 (0.09%) 
Skin lesion  1  1/2233 (0.04%) 
Skin mass  1  1/2233 (0.04%) 
Skin ulcer  1  2/2233 (0.09%) 
Surgical and medical procedures   
Stem cell transplant  1  1/2233 (0.04%) 
Vascular disorders   
Aortic aneurysm  1  2/2233 (0.09%) 
Aortic rupture  1  1/2233 (0.04%) 
Aortic stenosis  1  1/2233 (0.04%) 
Arterial disorder  1  2/2233 (0.09%) 
Arterial haemorrhage  1  1/2233 (0.04%) 
Circulatory collapse  1  2/2233 (0.09%) 
Deep vein thrombosis  1  10/2233 (0.45%) 
Embolism  1  1/2233 (0.04%) 
Haematoma  1  9/2233 (0.40%) 
Hyperaemia  1  1/2233 (0.04%) 
Hypertension  1  3/2233 (0.13%) 
Hypertensive crisis  1  1/2233 (0.04%) 
Hypotension  1  7/2233 (0.31%) 
Pallor  1  1/2233 (0.04%) 
Peripheral artery occlusion  1  1/2233 (0.04%) 
Peripheral artery stenosis  1  1/2233 (0.04%) 
Peripheral ischaemia  1  3/2233 (0.13%) 
Phlebitis  1  1/2233 (0.04%) 
Shock  1  1/2233 (0.04%) 
Thrombophlebitis superficial  1  1/2233 (0.04%) 
Venous thrombosis  1  1/2233 (0.04%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
INC424
Affected / at Risk (%)
Total   2008/2233 (89.92%) 
Blood and lymphatic system disorders   
Anaemia  1  1300/2233 (58.22%) 
Neutropenia  1  146/2233 (6.54%) 
Thrombocytopenia  1  990/2233 (44.33%) 
Gastrointestinal disorders   
Abdominal pain  1  149/2233 (6.67%) 
Constipation  1  121/2233 (5.42%) 
Diarrhoea  1  267/2233 (11.96%) 
Nausea  1  128/2233 (5.73%) 
General disorders   
Asthenia  1  331/2233 (14.82%) 
Fatigue  1  215/2233 (9.63%) 
Oedema peripheral  1  182/2233 (8.15%) 
Pyrexia  1  310/2233 (13.88%) 
Infections and infestations   
Herpes zoster  1  112/2233 (5.02%) 
Nasopharyngitis  1  115/2233 (5.15%) 
Urinary tract infection  1  114/2233 (5.11%) 
Investigations   
Alanine aminotransferase increased  1  134/2233 (6.00%) 
Platelet count decreased  1  198/2233 (8.87%) 
Weight increased  1  140/2233 (6.27%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  176/2233 (7.88%) 
Back pain  1  115/2233 (5.15%) 
Pain in extremity  1  147/2233 (6.58%) 
Nervous system disorders   
Headache  1  191/2233 (8.55%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  186/2233 (8.33%) 
Dyspnoea  1  155/2233 (6.94%) 
Skin and subcutaneous tissue disorders   
Pruritus  1  131/2233 (5.87%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01493414     History of Changes
Other Study ID Numbers: CINC424A2401
2010-024473-39 ( EudraCT Number )
First Submitted: December 13, 2011
First Posted: December 16, 2011
Results First Submitted: January 26, 2018
Results First Posted: April 26, 2019
Last Update Posted: April 26, 2019