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Trial record 5 of 14 for:    "Carcinoid Syndrome" | "Octreotide"

Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor (RADIANT-2)

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ClinicalTrials.gov Identifier: NCT00412061
Recruitment Status : Completed
First Posted : December 15, 2006
Results First Posted : March 12, 2012
Last Update Posted : November 21, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Carcinoid Tumor
Malignant Carcinoid Syndrome
Interventions Drug: Octreotide
Drug: Placebo
Drug: Everolimus
Enrollment 429
Recruitment Details  
Pre-assignment Details Total 429 patients were randomized to double blind phase of treatment. 170 patients moved to the Open Label Phase.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo Followed by Open Label Arm
Hide Arm/Group Description Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1. Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.
Period Title: Double Blind Phase
Started 216 213
Safety Set 215 [1] 211 [2]
Completed 0 0
Not Completed 216 213
Reason Not Completed
Disease Progression             101             154
Adverse Event             61             16
Final Primary Analysis             26             14
Withdrawal by Subject             18             20
Death             6             3
Protocol Violation             3             4
New Cander Therapy             1             1
Lost to Follow-up             0             1
[1]
1 patient did not provide at laest one valid post baseline safety assessment.
[2]
1 pt randomized never took drug Another randomized did not have valid post BL safety assessment
Period Title: Open Label Phase
Started 0 170
Completed 0 0
Not Completed 0 170
Reason Not Completed
Disease Progression             0             86
Adverse Event             0             46
Withdrawal by Subject             0             15
Administrative Problems             0             13
Death             0             7
Lost to Follow-up             0             2
New Cancer Therapy             0             1
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo Total
Hide Arm/Group Description Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1. Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Total of all reporting groups
Overall Number of Baseline Participants 216 213 429
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 216 participants 213 participants 429 participants
60.1  (10.72) 59.4  (11.13) 59.8  (10.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 216 participants 213 participants 429 participants
Female
119
  55.1%
89
  41.8%
208
  48.5%
Male
97
  44.9%
124
  58.2%
221
  51.5%
1.Primary Outcome
Title Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review
Hide Description Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary analysis of PFS was based on the independent central adjudicated assessment using Kaplan-Meier method.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all randomized patients.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Overall Number of Participants Analyzed 216 213
Median (95% Confidence Interval)
Unit of Measure: Months
16.43
(13.67 to 21.19)
11.33
(8.44 to 14.59)
2.Secondary Outcome
Title Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description The best overall response rate is defined as the percentage of patients having achieved confirmed Complete Response + Partial Response. Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. • Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS; Intent-to-treat Population) consists of all randomized patients.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Overall Number of Participants Analyzed 216 213
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
2.3
(0.8 to 5.30)
1.9
(0.5 to 4.7)
3.Secondary Outcome
Title Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level
Hide Description 5-HIAA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of 5-HIAA in urine were defined as ‘High’ if they exceeded the median value, and ‘Low’ if they were lower than or equal to the median.
Time Frame If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS; Intent-to-treat Population) consists of all randomized patients. This analysis includes PFS patients with non missing baseline 5-HIAA data.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Overall Number of Participants Analyzed 187 191
Median (95% Confidence Interval)
Unit of Measure: Months
5-HIAA <=median (n=93,96)
21.75 [1] 
(13.93 to NA)
13.90
(8.71 to 22.44)
5-HIAA > median (n=94,95)
13.83
(10.61 to 18.63)
8.41
(8.08 to 11.33)
[1]
Upper Limit was not applicable or computable as median was just reached.
4.Secondary Outcome
Title Overall Survival Using Kaplan-Meier Methodology
Hide Description Overall survival was defined as the time from the date of randomization to the date of death from any cause. If a patient was not known to have died, survival was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the median overall survival for each treatment group.
Time Frame Months 12, 24, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS; Intent-to-treat Population) consists of all randomized patients.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo Followed by Open Label Arm
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.
Overall Number of Participants Analyzed 216 213
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
12 Months
80.5
(74.5 to 85.3)
81.8
(75.8 to 86.4)
24 Months
57.0
(49.9 to 63.4)
63.6
(56.6 to 69.8)
36 Months
42.9
(36.0 to 49.6)
48.5
(41.4 to 55.3)
48 Months
38.0
(31.2 to 44.7)
41.6
(34.6 to 48.5)
5.Secondary Outcome
Title Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)
Hide Description AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame From first day of treatment up to 28 days after last day of treatment in double blind
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients who received at least one dose of study drug and who had at least one valid post-baseline safety assessment.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Overall Number of Participants Analyzed 215 211
Measure Type: Number
Unit of Measure: Patients
Clinically notable AE 208 146
Grade 3-4 Adverse Events 162 109
On treatment death 19 11
Serious adverse events 126 74
6.Secondary Outcome
Title Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)
Hide Description AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame From first day of treatment up to 28 days after last day of treatment in double blind
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients who received at least one dose of study drug and who had at least one valid post-baseline safety assessment.
Arm/Group Title Everolimus Open Label Arm
Hide Arm/Group Description:
Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.
Overall Number of Participants Analyzed 170
Measure Type: Number
Unit of Measure: Patients
Clinically notable AE 154
Grade 3-4 Adverse Events 115
On treatment death 22
Serious adverse events 93
7.Secondary Outcome
Title Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)
Hide Description Serum CgA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of serum CgA were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be ‘Elevated’; otherwise considered as "Non-elevated".
Time Frame If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS; Intent-to-treat Population) consists of all randomized patients. This analysis includes PFS patients with non missing baseline CgA data.
Arm/Group Title Octreotide+ Everolimus Octreotide+ Placebo
Hide Arm/Group Description:
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Overall Number of Participants Analyzed 212 208
Median (95% Confidence Interval)
Unit of Measure: Months
CgA<=2x ULN (n=60,78)
31.31 [1] 
(19.32 to NA)
20.07 [1] 
(13.04 to NA)
CgA>2x ULN (n=152,130)
13.93
(11.30 to 17.08)
8.41
(7.72 to 11.14)
[1]
Upper Limit was not applicable or computable as median was just reached.
Time Frame [Not Specified]
Adverse Event Reporting Description Double blind period, Safety Set consists all patients received at least one dose of study drug and who had at least one valid post-baseline safety assessment. The Open-label Set consists all patients received at least one dose of open-label everolimus and who had at least one valid safety assessment after initiation of open-label treatment
 
Arm/Group Title Everolimus + Octreotide Placebo + Octreotide Everolimus Open Label
Hide Arm/Group Description Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1. Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.
All-Cause Mortality
Everolimus + Octreotide Placebo + Octreotide Everolimus Open Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus + Octreotide Placebo + Octreotide Everolimus Open Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   126/215 (58.60%)   74/211 (35.07%)   93/170 (54.71%) 
Blood and lymphatic system disorders       
Anaemia  1  4/215 (1.86%)  2/211 (0.95%)  4/170 (2.35%) 
Disseminated intravascular coagulation  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Febrile neutropenia  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Haemorrhagic anaemia  1  0/215 (0.00%)  1/211 (0.47%)  2/170 (1.18%) 
Leukopenia  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Pancytopenia  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Thrombocytopenia  1  3/215 (1.40%)  0/211 (0.00%)  1/170 (0.59%) 
Cardiac disorders       
Acute myocardial infarction  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Angina pectoris  1  2/215 (0.93%)  3/211 (1.42%)  1/170 (0.59%) 
Aortic valve incompetence  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Arrhythmia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Atrial fibrillation  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Atrial flutter  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Carcinoid heart disease  1  2/215 (0.93%)  2/211 (0.95%)  2/170 (1.18%) 
Cardiac arrest  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Cardiac failure  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Cardiac failure congestive  1  2/215 (0.93%)  2/211 (0.95%)  0/170 (0.00%) 
Cardiac valve disease  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Cardio-respiratory arrest  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Cardiopulmonary failure  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Coronary artery disease  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Coronary artery occlusion  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Dilatation ventricular  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Left ventricular dysfunction  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Mitral valve stenosis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Myocardial infarction  1  1/215 (0.47%)  2/211 (0.95%)  1/170 (0.59%) 
Myocardial ischaemia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Palpitations  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Pericardial effusion  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Pulmonary valve incompetence  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Pulmonary valve stenosis  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Right ventricular failure  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Stress cardiomyopathy  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Tachycardia paroxysmal  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Tricuspid valve disease  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Tricuspid valve incompetence  1  1/215 (0.47%)  2/211 (0.95%)  0/170 (0.00%) 
Tricuspid valve prolapse  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Tricuspid valve stenosis  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Congenital, familial and genetic disorders       
Atrial septal defect  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Endocrine disorders       
Adrenocortical insufficiency acute  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Carcinoid crisis  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Carcinoid syndrome  1  2/215 (0.93%)  1/211 (0.47%)  2/170 (1.18%) 
Eye disorders       
Diplopia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Gastrointestinal disorders       
Abdominal adhesions  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Abdominal distension  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Abdominal hernia  1  1/215 (0.47%)  1/211 (0.47%)  1/170 (0.59%) 
Abdominal pain  1  15/215 (6.98%)  11/211 (5.21%)  11/170 (6.47%) 
Abdominal pain lower  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Abdominal pain upper  1  1/215 (0.47%)  2/211 (0.95%)  1/170 (0.59%) 
Ascites  1  0/215 (0.00%)  5/211 (2.37%)  0/170 (0.00%) 
Colitis  1  2/215 (0.93%)  0/211 (0.00%)  1/170 (0.59%) 
Constipation  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Diarrhoea  1  9/215 (4.19%)  5/211 (2.37%)  7/170 (4.12%) 
Duodenal obstruction  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Duodenal stenosis  1  0/215 (0.00%)  1/211 (0.47%)  2/170 (1.18%) 
Enteritis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Faeces discoloured  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Food poisoning  1  0/215 (0.00%)  2/211 (0.95%)  0/170 (0.00%) 
Gastric haemorrhage  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Gastric ulcer  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Gastritis erosive  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Gastrointestinal angiodysplasia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Gastrointestinal fistula  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Gastrointestinal haemorrhage  1  1/215 (0.47%)  1/211 (0.47%)  2/170 (1.18%) 
Gastrooesophageal reflux disease  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Haematemesis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Haematochezia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Haemorrhoids  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Ileus  1  5/215 (2.33%)  1/211 (0.47%)  0/170 (0.00%) 
Inguinal hernia, obstructive  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Intestinal angina  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Intestinal obstruction  1  2/215 (0.93%)  5/211 (2.37%)  3/170 (1.76%) 
Intestinal perforation  1  0/215 (0.00%)  0/211 (0.00%)  2/170 (1.18%) 
Lip oedema  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Melaena  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Nausea  1  4/215 (1.86%)  4/211 (1.90%)  2/170 (1.18%) 
Oesophageal spasm  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Pancreatitis acute  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Pneumatosis intestinalis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Rectal haemorrhage  1  3/215 (1.40%)  0/211 (0.00%)  1/170 (0.59%) 
Retroperitoneal haematoma  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Small intestinal haemorrhage  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Small intestinal obstruction  1  8/215 (3.72%)  3/211 (1.42%)  4/170 (2.35%) 
Small intestinal stenosis  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Stomatitis  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Subileus  1  3/215 (1.40%)  2/211 (0.95%)  0/170 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Vomiting  1  7/215 (3.26%)  6/211 (2.84%)  5/170 (2.94%) 
General disorders       
Asthenia  1  2/215 (0.93%)  3/211 (1.42%)  1/170 (0.59%) 
Brain death  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Chest pain  1  1/215 (0.47%)  1/211 (0.47%)  1/170 (0.59%) 
Chills  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Face oedema  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Fatigue  1  2/215 (0.93%)  1/211 (0.47%)  0/170 (0.00%) 
General physical health deterioration  1  6/215 (2.79%)  3/211 (1.42%)  5/170 (2.94%) 
Generalised oedema  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Hypothermia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Malaise  1  2/215 (0.93%)  1/211 (0.47%)  0/170 (0.00%) 
Non-cardiac chest pain  1  3/215 (1.40%)  0/211 (0.00%)  0/170 (0.00%) 
Oedema peripheral  1  3/215 (1.40%)  4/211 (1.90%)  3/170 (1.76%) 
Pain  1  1/215 (0.47%)  2/211 (0.95%)  0/170 (0.00%) 
Performance status decreased  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Pyrexia  1  8/215 (3.72%)  3/211 (1.42%)  3/170 (1.76%) 
Spinal pain  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Sudden death  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Cholangitis  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Cholangitis acute  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Cholecystitis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Cholecystitis acute  1  2/215 (0.93%)  0/211 (0.00%)  1/170 (0.59%) 
Cholelithiasis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Cholestasis  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Hepatic failure  1  2/215 (0.93%)  1/211 (0.47%)  0/170 (0.00%) 
Hepatic function abnormal  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Hepatocellular injury  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Hepatotoxicity  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Hyperbilirubinaemia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Jaundice  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Immune system disorders       
Drug hypersensitivity  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Infections and infestations       
Abdominal wall abscess  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Abscess intestinal  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Arthritis infective  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Aspergillosis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Bacteraemia  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Bronchiolitis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Bronchopneumonia  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Cellulitis  1  3/215 (1.40%)  0/211 (0.00%)  0/170 (0.00%) 
Cholecystitis infective  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Clostridium difficile colitis  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Diverticulitis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Erysipelas  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Escherichia sepsis  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Gastroenteritis  1  2/215 (0.93%)  1/211 (0.47%)  2/170 (1.18%) 
Gastroenteritis viral  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Herpes zoster  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Infected skin ulcer  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Infection  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Influenza  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Localised infection  1  0/215 (0.00%)  0/211 (0.00%)  2/170 (1.18%) 
Lung infection  1  1/215 (0.47%)  0/211 (0.00%)  2/170 (1.18%) 
Osteomyelitis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Peritonitis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Pneumonia  1  9/215 (4.19%)  1/211 (0.47%)  5/170 (2.94%) 
Pneumonia viral  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Sepsis  1  2/215 (0.93%)  1/211 (0.47%)  4/170 (2.35%) 
Sinusitis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Staphylococcal infection  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Urinary tract infection  1  2/215 (0.93%)  2/211 (0.95%)  0/170 (0.00%) 
Urinary tract infection bacterial  1  0/215 (0.00%)  2/211 (0.95%)  0/170 (0.00%) 
Urosepsis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Injury, poisoning and procedural complications       
Bone fissure  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Femoral neck fracture  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Fractured sacrum  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Heat exhaustion  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Hip fracture  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Humerus fracture  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Joint injury  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Post procedural complication  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Post procedural haemorrhage  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Pulmonary contusion  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Rib fracture  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Scapula fracture  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Seroma  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Toxicity to various agents  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Traumatic intracranial haemorrhage  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Investigations       
Alanine aminotransferase increased  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Aspartate aminotransferase increased  1  2/215 (0.93%)  0/211 (0.00%)  1/170 (0.59%) 
Blood alkaline phosphatase increased  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Blood creatinine increased  1  2/215 (0.93%)  0/211 (0.00%)  4/170 (2.35%) 
Blood urea increased  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Cardiac murmur  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Coagulation time shortened  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Heart rate increased  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Lipase increased  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Weight decreased  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Metabolism and nutrition disorders       
Cachexia  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Decreased appetite  1  0/215 (0.00%)  1/211 (0.47%)  2/170 (1.18%) 
Dehydration  1  7/215 (3.26%)  1/211 (0.47%)  3/170 (1.76%) 
Failure to thrive  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Hypercalcaemia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Hyperglycaemia  1  2/215 (0.93%)  0/211 (0.00%)  3/170 (1.76%) 
Hypocalcaemia  1  2/215 (0.93%)  0/211 (0.00%)  1/170 (0.59%) 
Hypoglycaemia  1  2/215 (0.93%)  1/211 (0.47%)  0/170 (0.00%) 
Hypokalaemia  1  4/215 (1.86%)  0/211 (0.00%)  1/170 (0.59%) 
Hypomagnesaemia  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Hypophosphataemia  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Malnutrition  1  1/215 (0.47%)  2/211 (0.95%)  0/170 (0.00%) 
Metabolic acidosis  1  2/215 (0.93%)  0/211 (0.00%)  1/170 (0.59%) 
Type 2 diabetes mellitus  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Arthritis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Back pain  1  0/215 (0.00%)  4/211 (1.90%)  1/170 (0.59%) 
Bone pain  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Flank pain  1  2/215 (0.93%)  1/211 (0.47%)  0/170 (0.00%) 
Muscle spasms  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Musculoskeletal chest pain  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Neck pain  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Osteoarthritis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Osteoporosis  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Pain in extremity  1  2/215 (0.93%)  0/211 (0.00%)  0/170 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-cell type acute leukaemia  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Brain neoplasm malignant  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Cancer pain  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Glioblastoma  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Lung infiltration malignant  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Malignant pleural effusion  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Metastatic pain  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Pancreatic carcinoma  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Tumour compression  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Nervous system disorders       
Cerebral ischaemia  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Cerebrovascular accident  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Convulsion  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Depressed level of consciousness  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Dizziness postural  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Encephalopathy  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Facial paresis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Grand mal convulsion  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Headache  1  0/215 (0.00%)  2/211 (0.95%)  0/170 (0.00%) 
Hypoaesthesia  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Intracranial haematoma  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Lethargy  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Mental impairment  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Metabolic encephalopathy  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Radicular syndrome  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Radiculopathy  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Sciatica  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Subarachnoid haemorrhage  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Syncope  1  2/215 (0.93%)  1/211 (0.47%)  2/170 (1.18%) 
Psychiatric disorders       
Confusional state  1  1/215 (0.47%)  1/211 (0.47%)  1/170 (0.59%) 
Depression  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Hallucination  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Mental status changes  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Renal and urinary disorders       
Bladder tamponade  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Calculus ureteric  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Calculus urinary  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Eosinophilic cystitis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Haematuria  1  0/215 (0.00%)  1/211 (0.47%)  1/170 (0.59%) 
Hydronephrosis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Nephrolithiasis  1  1/215 (0.47%)  1/211 (0.47%)  2/170 (1.18%) 
Renal failure  1  4/215 (1.86%)  0/211 (0.00%)  3/170 (1.76%) 
Renal failure acute  1  3/215 (1.40%)  1/211 (0.47%)  1/170 (0.59%) 
Renal failure chronic  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Renal impairment  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Renal infarct  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Ureteric obstruction  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Urinary bladder haemorrhage  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Urinary retention  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Reproductive system and breast disorders       
Testicular swelling  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Atelectasis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Cough  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Dyspnoea  1  8/215 (3.72%)  2/211 (0.95%)  1/170 (0.59%) 
Granulomatous pneumonitis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Haemoptysis  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Hypoxia  1  3/215 (1.40%)  1/211 (0.47%)  0/170 (0.00%) 
Interstitial lung disease  1  3/215 (1.40%)  0/211 (0.00%)  1/170 (0.59%) 
Laryngeal oedema  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Lung infiltration  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Organising pneumonia  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Pleural effusion  1  3/215 (1.40%)  0/211 (0.00%)  2/170 (1.18%) 
Pneumonitis  1  2/215 (0.93%)  0/211 (0.00%)  2/170 (1.18%) 
Pneumothorax  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Pulmonary embolism  1  6/215 (2.79%)  1/211 (0.47%)  3/170 (1.76%) 
Pulmonary hypertension  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Respiratory arrest  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Respiratory distress  1  0/215 (0.00%)  0/211 (0.00%)  1/170 (0.59%) 
Respiratory failure  1  1/215 (0.47%)  1/211 (0.47%)  0/170 (0.00%) 
Tachypnoea  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Skin and subcutaneous tissue disorders       
Angioedema  1  1/215 (0.47%)  0/211 (0.00%)  1/170 (0.59%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Vascular disorders       
Aortic dissection  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Deep vein thrombosis  1  1/215 (0.47%)  1/211 (0.47%)  2/170 (1.18%) 
Flushing  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Haematoma  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Hypertension  1  1/215 (0.47%)  1/211 (0.47%)  1/170 (0.59%) 
Hypotension  1  0/215 (0.00%)  1/211 (0.47%)  0/170 (0.00%) 
Jugular vein thrombosis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Orthostatic hypotension  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Phlebitis  1  1/215 (0.47%)  0/211 (0.00%)  0/170 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Everolimus + Octreotide Placebo + Octreotide Everolimus Open Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   214/215 (99.53%)   194/211 (91.94%)   162/170 (95.29%) 
Blood and lymphatic system disorders       
Anaemia  1  58/215 (26.98%)  21/211 (9.95%)  34/170 (20.00%) 
Leukopenia  1  16/215 (7.44%)  2/211 (0.95%)  2/170 (1.18%) 
Neutropenia  1  18/215 (8.37%)  3/211 (1.42%)  13/170 (7.65%) 
Thrombocytopenia  1  34/215 (15.81%)  1/211 (0.47%)  15/170 (8.82%) 
Gastrointestinal disorders       
Abdominal distension  1  12/215 (5.58%)  12/211 (5.69%)  10/170 (5.88%) 
Abdominal pain  1  65/215 (30.23%)  68/211 (32.23%)  43/170 (25.29%) 
Abdominal pain upper  1  22/215 (10.23%)  26/211 (12.32%)  16/170 (9.41%) 
Aphthous stomatitis  1  28/215 (13.02%)  3/211 (1.42%)  15/170 (8.82%) 
Ascites  1  17/215 (7.91%)  9/211 (4.27%)  8/170 (4.71%) 
Constipation  1  31/215 (14.42%)  22/211 (10.43%)  17/170 (10.00%) 
Diarrhoea  1  114/215 (53.02%)  77/211 (36.49%)  77/170 (45.29%) 
Dry mouth  1  22/215 (10.23%)  6/211 (2.84%)  7/170 (4.12%) 
Dysphagia  1  15/215 (6.98%)  5/211 (2.37%)  4/170 (2.35%) 
Flatulence  1  27/215 (12.56%)  28/211 (13.27%)  12/170 (7.06%) 
Haemorrhoids  1  17/215 (7.91%)  9/211 (4.27%)  9/170 (5.29%) 
Mouth ulceration  1  17/215 (7.91%)  5/211 (2.37%)  11/170 (6.47%) 
Nausea  1  92/215 (42.79%)  63/211 (29.86%)  60/170 (35.29%) 
Stomatitis  1  109/215 (50.70%)  25/211 (11.85%)  63/170 (37.06%) 
Vomiting  1  69/215 (32.09%)  40/211 (18.96%)  30/170 (17.65%) 
General disorders       
Asthenia  1  51/215 (23.72%)  30/211 (14.22%)  30/170 (17.65%) 
Chills  1  15/215 (6.98%)  10/211 (4.74%)  5/170 (2.94%) 
Fatigue  1  103/215 (47.91%)  91/211 (43.13%)  63/170 (37.06%) 
Oedema peripheral  1  92/215 (42.79%)  47/211 (22.27%)  62/170 (36.47%) 
Pyrexia  1  42/215 (19.53%)  21/211 (9.95%)  32/170 (18.82%) 
Infections and infestations       
Bronchitis  1  11/215 (5.12%)  7/211 (3.32%)  8/170 (4.71%) 
Nasopharyngitis  1  19/215 (8.84%)  26/211 (12.32%)  19/170 (11.18%) 
Sinusitis  1  12/215 (5.58%)  9/211 (4.27%)  17/170 (10.00%) 
Upper respiratory tract infection  1  27/215 (12.56%)  12/211 (5.69%)  11/170 (6.47%) 
Urinary tract infection  1  27/215 (12.56%)  16/211 (7.58%)  19/170 (11.18%) 
Investigations       
Alanine aminotransferase increased  1  9/215 (4.19%)  6/211 (2.84%)  10/170 (5.88%) 
Aspartate aminotransferase increased  1  11/215 (5.12%)  8/211 (3.79%)  8/170 (4.71%) 
Blood creatinine increased  1  15/215 (6.98%)  5/211 (2.37%)  8/170 (4.71%) 
Weight decreased  1  59/215 (27.44%)  31/211 (14.69%)  33/170 (19.41%) 
Metabolism and nutrition disorders       
Decreased appetite  1  64/215 (29.77%)  36/211 (17.06%)  33/170 (19.41%) 
Dehydration  1  17/215 (7.91%)  12/211 (5.69%)  9/170 (5.29%) 
Hypercholesterolaemia  1  17/215 (7.91%)  6/211 (2.84%)  7/170 (4.12%) 
Hyperglycaemia  1  42/215 (19.53%)  9/211 (4.27%)  24/170 (14.12%) 
Hyperlipidaemia  1  15/215 (6.98%)  3/211 (1.42%)  4/170 (2.35%) 
Hypocalcaemia  1  17/215 (7.91%)  4/211 (1.90%)  11/170 (6.47%) 
Hypokalaemia  1  50/215 (23.26%)  8/211 (3.79%)  27/170 (15.88%) 
Hypomagnesaemia  1  15/215 (6.98%)  5/211 (2.37%)  6/170 (3.53%) 
Hypophosphataemia  1  11/215 (5.12%)  6/211 (2.84%)  8/170 (4.71%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  38/215 (17.67%)  28/211 (13.27%)  19/170 (11.18%) 
Back pain  1  33/215 (15.35%)  41/211 (19.43%)  18/170 (10.59%) 
Muscle spasms  1  17/215 (7.91%)  13/211 (6.16%)  10/170 (5.88%) 
Musculoskeletal chest pain  1  18/215 (8.37%)  7/211 (3.32%)  11/170 (6.47%) 
Musculoskeletal pain  1  21/215 (9.77%)  21/211 (9.95%)  8/170 (4.71%) 
Myalgia  1  16/215 (7.44%)  14/211 (6.64%)  8/170 (4.71%) 
Pain in extremity  1  32/215 (14.88%)  24/211 (11.37%)  19/170 (11.18%) 
Nervous system disorders       
Dizziness  1  29/215 (13.49%)  24/211 (11.37%)  12/170 (7.06%) 
Dysgeusia  1  42/215 (19.53%)  12/211 (5.69%)  30/170 (17.65%) 
Headache  1  65/215 (30.23%)  49/211 (23.22%)  32/170 (18.82%) 
Psychiatric disorders       
Anxiety  1  14/215 (6.51%)  14/211 (6.64%)  12/170 (7.06%) 
Depression  1  16/215 (7.44%)  11/211 (5.21%)  12/170 (7.06%) 
Insomnia  1  20/215 (9.30%)  15/211 (7.11%)  12/170 (7.06%) 
Renal and urinary disorders       
Dysuria  1  12/215 (5.58%)  5/211 (2.37%)  7/170 (4.12%) 
Pollakiuria  1  10/215 (4.65%)  6/211 (2.84%)  11/170 (6.47%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  59/215 (27.44%)  32/211 (15.17%)  38/170 (22.35%) 
Dyspnoea  1  59/215 (27.44%)  19/211 (9.00%)  27/170 (15.88%) 
Dyspnoea exertional  1  9/215 (4.19%)  11/211 (5.21%)  7/170 (4.12%) 
Epistaxis  1  33/215 (15.35%)  5/211 (2.37%)  24/170 (14.12%) 
Oropharyngeal pain  1  20/215 (9.30%)  6/211 (2.84%)  13/170 (7.65%) 
Pleural effusion  1  12/215 (5.58%)  6/211 (2.84%)  7/170 (4.12%) 
Pneumonitis  1  20/215 (9.30%)  2/211 (0.95%)  6/170 (3.53%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  13/215 (6.05%)  4/211 (1.90%)  7/170 (4.12%) 
Dry skin  1  23/215 (10.70%)  5/211 (2.37%)  9/170 (5.29%) 
Erythema  1  17/215 (7.91%)  4/211 (1.90%)  7/170 (4.12%) 
Hyperhidrosis  1  9/215 (4.19%)  13/211 (6.16%)  5/170 (2.94%) 
Onychoclasis  1  11/215 (5.12%)  1/211 (0.47%)  10/170 (5.88%) 
Pruritus  1  42/215 (19.53%)  12/211 (5.69%)  18/170 (10.59%) 
Rash  1  88/215 (40.93%)  37/211 (17.54%)  59/170 (34.71%) 
Vascular disorders       
Flushing  1  20/215 (9.30%)  20/211 (9.48%)  6/170 (3.53%) 
Hypertension  1  24/215 (11.16%)  21/211 (9.95%)  16/170 (9.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
Results Point of Contact
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Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
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Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00412061     History of Changes
Other Study ID Numbers: CRAD001C2325
2006-004507-18 ( EudraCT Number )
First Submitted: December 13, 2006
First Posted: December 15, 2006
Results First Submitted: October 25, 2011
Results First Posted: March 12, 2012
Last Update Posted: November 21, 2014