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Trial record 34 of 40 for:    somatostatin analogues | Neuroendocrine Tumors

Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease

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ClinicalTrials.gov Identifier: NCT00690430
Recruitment Status : Completed
First Posted : June 4, 2008
Results First Posted : July 30, 2013
Last Update Posted : July 30, 2013
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Symptomatic Refractory Resistant Carcinoid Disease
Interventions Drug: Pasireotide
Drug: Octreotide
Enrollment 186
Recruitment Details 186 patients were screened and 110 were randomized into the study.
Pre-assignment Details  
Arm/Group Title Pasireotide LAR Octreotide LAR Extension: Octreotide LAR/Pasireotide LAR
Hide Arm/Group Description Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed. Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed. After 6 month double blind core period, non-responders on Octreotide were given option to cross over to Pasireotide LAR in the Extension Phase of study.
Period Title: Core Phase
Started 53 [1] 57 0 [2]
Completed 35 34 0
Not Completed 18 23 0
Reason Not Completed
Abnormal Laboratory value             0             1             0
Adverse Event             5             1             0
Death             0             2             0
Protocol Violation             1             0             0
Withdrawal by Subject             3             3             0
Subject no longer requires study drug             1             0             0
Lack of Efficacy             8             10             0
Administrative Problems             0             1             0
Early Termination             0             5             0
[1]
"Started" indicates Full Analysis Set (FAS) and Safety Set.
[2]
This arm belongs to Extension Phase.
Period Title: Extension Phase
Started 20 [1] 6 [1] 15 [1]
Completed 2 1 2
Not Completed 18 5 13
Reason Not Completed
Lack of Efficacy             3             1             4
Abnormal Lab Values             1             0             0
Abnormal test procedure results             1             0             0
Administrative Problems             0             1             1
Adverse Event             2             1             2
Death             1             1             1
Withdrawal by Subject             0             0             2
Early Termination             10             1             3
[1]
Only those patients (except from UK) who received clinical benefit could extend therapy in extension
Arm/Group Title Pasireotide LAR Octreotide LAR Total
Hide Arm/Group Description Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed. Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed. Total of all reporting groups
Overall Number of Baseline Participants 53 57 110
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 53 participants 57 participants 110 participants
61.2  (9.21) 62.8  (11.91) 62  (10.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 57 participants 110 participants
Female
24
  45.3%
23
  40.4%
47
  42.7%
Male
29
  54.7%
34
  59.6%
63
  57.3%
1.Primary Outcome
Title Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
Hide Description Percentage of patients who received clinical benefit in symptom (diarrhea and/or flushing) improvement as: Diarrhea (D)+Flushing (F): Patients with a daily mean number (#) of at least four bowel movements and a total of five or more flushing episodes. Clinical Benefit Response Criteria (CBRC): <4 daily mean bowel movements AND at least 20% reduction from Baseline in the daily mean # of bowel movements AND any reduction in the total # of flushing episodes compared with Baseline. (D) Patients with a daily mean # of at least four bowel movements and a total # of <5 flushing episodes. (CBRC) <4 daily mean bowel movements AND at least a 20% reduction from Baseline in the daily mean # of bowel movements. (F) Patients with a total # of at least 14 flushing episodes and a daily mean # of <4 bowel movements (CBRC) At least a 30% reduction from Baseline in the total # of flushing episodes.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analyzable set consists of subset of FAS patients who were randomized at least six months prior to futility interim analysis data cut-off. It is for the primary efficacy analysis and secondary efficacy analysis except for tumor response assessment. Data reported was based on randomized patients at the time of the interim analysis.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 43 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Diarrhea and Flushing (N=37, 39)
13.5
(4.5 to 28.8)
28.2
(15.0 to 44.9)
Diarrhea (N=2, 5)
100
(15.8 to 100)
20.0
(0.5 to 71.6)
Flushing (N=4, 1)
50
(6.8 to 93.2)
0.0
(0.0 to 97.5)
Overall (N=43, 45)
20.9
(10.0 to 36.0)
26.7
(14.6 to 41.9)
2.Secondary Outcome
Title Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.
Hide Description Percent change from Baseline in mean daily bowel movements at Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. mean daily bowel movement at Baseline) and randomization stratum (D+F or D) as covariates. Percentage change = (Month 6 - baseline)/baseline.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analyzable set consists of the subset of FAS patients who were randomized at least six months prior to the futility DMC data cut-off. Patients who had symptoms at baseline and at 6 months were included in this analysis.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 26 32
Mean (Standard Deviation)
Unit of Measure: Percentage of Episodes
Diarrhea and Flushing (N=24, 28) -23.5  (24.28) -38.4  (28.74)
Predominantly Diarrhea (D) (N=2, 4) -44.2  (10.26) -22.9  (31.68)
Overall (N=26, 32) -25.1  (24.04) -36.5  (29.05)
3.Secondary Outcome
Title Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.
Hide Description Percent change from Baseline in total number of flushing episodes comprising Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. total number of flushing episodes at Baseline) and randomization stratum (D+F or F) as covariates.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy analyzable set consists of the subset of FAS patients who were randomized at least six months prior to the futility DMC data cut-off. Patients were analyzed according the treatment they were assigned to at randomization. (ITT) principle.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 28 29
Mean (Standard Deviation)
Unit of Measure: Percentage of Episodes
Diarrhea and Flushing (N=24, 28) -41.0  (41.06) -52.8  (32.18)
Predominately Flushing (N=4, 1) -48.4  (23.13) 47.2 [1]   (NA)
Overall (N=28, 29) -42.1  (38.76) -49.4  (36.65)
[1]
Standard Deviation could not be calculated because there was only 1 patient analyzed.
4.Secondary Outcome
Title Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.
Hide Description [Not Specified]
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Objective Tumor Response Rate Assessed by Investigator
Hide Description Baseline evaluations were to include Triphasic CT scan or MRI of the abdomen. Triphasic CT or MRIs were to be read by same radiologist at each assessment, measuring the same target and non-target lesions and accounting for all lesions that were present at Baseline. All known disease was accounted for when assessing objective tumor status. Current objective tumor status was to be captured on Tumor Assessment CRF. Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consists of all patients randomized into the study. Patients were analyzed according to the treatment they were assigned to at randomization. Patients randomized 6 months before the final clinical cutoff date were included in this analysis.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 51 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
2.0
(0.0 to 10.4)
3.8
(0.5 to 13.2)
6.Secondary Outcome
Title Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria
Hide Description Disease control rate (DCR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline, or a new lesion; or progression of non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consists of all patients randomized into the study. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. Patients with analyzable data at month 6 were included in this analysis.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 51 52
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
62.7
(48.1 to 75.9)
46.2
(32.2 to 60.5)
7.Secondary Outcome
Title Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire
Hide Description [Not Specified]
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression
Hide Description [Not Specified]
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response
Hide Description [Not Specified]
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements
Hide Description [Not Specified]
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.
Arm/Group Title Pasireotide LAR Octreotide LAR
Hide Arm/Group Description:
Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.
Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pasireotide LAR Octreotide LAR Extension Phase Pasireotide LAR Extension Phase Octreotide LAR Crossover to Pasireotide LAR
Hide Arm/Group Description Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed. Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed. Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed. Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed. After 6 month double blind core period, non-responders on Octreotide were given option to cross over to Pasireotide LAR in the Extension Phase of study.
All-Cause Mortality
Pasireotide LAR Octreotide LAR Extension Phase Pasireotide LAR Extension Phase Octreotide LAR Crossover to Pasireotide LAR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pasireotide LAR Octreotide LAR Extension Phase Pasireotide LAR Extension Phase Octreotide LAR Crossover to Pasireotide LAR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/53 (28.30%)   19/57 (33.33%)   9/20 (45.00%)   2/6 (33.33%)   7/15 (46.67%) 
Cardiac disorders           
Carcinoid heart disease  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cardiac failure  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Cardiomyopathy  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Endocardial fibrosis  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Sinus bradycardia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Tricuspid valve incompetence  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  3/53 (5.66%)  3/57 (5.26%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Anorectal disorder  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Colitis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Diarrhea  1  4/53 (7.55%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Ileus  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Intestinal infarction  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Intestinal perforation  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Mesenteric vein thrombosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Nausea  1  0/53 (0.00%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Oesophageal varices haemorrhage  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Pneumoperitoneum  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Vomiting  1  1/53 (1.89%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
General disorders           
Asthenia  1  0/53 (0.00%)  2/57 (3.51%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Chest pain  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Condition aggravated  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Device dislocation  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Device infusion issue  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Fatigue  1  2/53 (3.77%)  2/57 (3.51%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
General physical health deterioration  1  1/53 (1.89%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Localised oedema  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Malaise  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Medical device complication  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Oedema peripheral  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hepatobiliary disorders           
Cholangitis  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cholecystitis  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cholestasis  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hepatic failure  1  0/53 (0.00%)  2/57 (3.51%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Hepatomegaly  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Infections and infestations           
Clostridial infection  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Device related infection  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Infectious peritonitis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Urinary tract infection  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Injury, poisoning and procedural complications           
Humerus fracture  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Procedural pain  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Tendon rupture  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Investigations           
Alanine aminotransferase increased  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Aspartate aminotransferase increased  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood alkaline phosphatase increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood bicarbonate decreased  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood creatinine increased  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood pH increased  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gamma-glutamyltransferase increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hepatic enzyme increased  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Liver function test abnormal  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Troponin increased  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Weight decreased  1  2/53 (3.77%)  2/57 (3.51%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  0/53 (0.00%)  2/57 (3.51%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dehydration  1  2/53 (3.77%)  2/57 (3.51%)  1/20 (5.00%)  1/6 (16.67%)  1/15 (6.67%) 
Diabetes mellitus  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hyperglycaemia  1  4/53 (7.55%)  0/57 (0.00%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Hyperkalaemia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypoglycaemia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypokalaemia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hyponatraemia  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypovolaemia  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Malnutrition  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Metabolic acidosis  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Type 2 diabetes mellitus  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders           
Bone pain  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Intervertebral disc disorder  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Pain in extremity  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Carcinoid tumour  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Carcinoid tumour of the gastrointestinal tract  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Metastases to chest wall  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Metastatic carcinoid tumour  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Neoplasm malignant  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Nervous system disorders           
Central nervous system lesion  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hemiparesis  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Psychiatric disorders           
Confusional state  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Renal and urinary disorders           
Nephritis  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Renal failure  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Renal failure acute  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Renal failure chronic  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Urinary tract disorder  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pleural effusion  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Pulmonary embolism  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Social circumstances           
Respite care  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Vascular disorders           
Flushing  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Orthostatic hypotension  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Vein disorder  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
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%
Pasireotide LAR Octreotide LAR Extension Phase Pasireotide LAR Extension Phase Octreotide LAR Crossover to Pasireotide LAR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/53 (94.34%)   48/57 (84.21%)   19/20 (95.00%)   5/6 (83.33%)   12/15 (80.00%) 
Blood and lymphatic system disorders           
Anaemia  1  3/53 (5.66%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Leukocytosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cardiac disorders           
Aortic valve sclerosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Atrial fibrillation  1  0/53 (0.00%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Bradycardia  1  2/53 (3.77%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Bundle branch block right  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Coronary artery disease  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dilatation ventricular  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Mitral valve incompetence  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Palpitations  1  0/53 (0.00%)  5/57 (8.77%)  0/20 (0.00%)  0/6 (0.00%)  2/15 (13.33%) 
Pulmonary valve incompetence  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Tricuspid valve incompetence  1  2/53 (3.77%)  3/57 (5.26%)  1/20 (5.00%)  0/6 (0.00%)  2/15 (13.33%) 
Congenital, familial and genetic disorders           
Birth mark  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Endocrine disorders           
Hypothyroidism  1  0/53 (0.00%)  0/57 (0.00%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Eye disorders           
Conjunctivitis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dry eye  1  2/53 (3.77%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Eye pain  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Glaucoma  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Visual impairment  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gastrointestinal disorders           
Abdominal distension  1  3/53 (5.66%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Abdominal pain  1  8/53 (15.09%)  8/57 (14.04%)  1/20 (5.00%)  0/6 (0.00%)  3/15 (20.00%) 
Abdominal pain lower  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Abdominal pain upper  1  2/53 (3.77%)  3/57 (5.26%)  2/20 (10.00%)  1/6 (16.67%)  0/15 (0.00%) 
Anal fissure  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Anal haemorrhage  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Constipation  1  0/53 (0.00%)  4/57 (7.02%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Diarrhoea  1  12/53 (22.64%)  9/57 (15.79%)  4/20 (20.00%)  0/6 (0.00%)  2/15 (13.33%) 
Dry mouth  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Duodenal ulcer  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dyspepsia  1  3/53 (5.66%)  3/57 (5.26%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Dysphagia  1  0/53 (0.00%)  0/57 (0.00%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Faecal incontinence  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Flatulence  1  7/53 (13.21%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gastritis  1  0/53 (0.00%)  1/57 (1.75%)  3/20 (15.00%)  0/6 (0.00%)  1/15 (6.67%) 
Gastrointestinal haemorrhage  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Haematochezia  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Haemorrhoids  1  1/53 (1.89%)  2/57 (3.51%)  4/20 (20.00%)  0/6 (0.00%)  0/15 (0.00%) 
Nausea  1  10/53 (18.87%)  7/57 (12.28%)  4/20 (20.00%)  0/6 (0.00%)  3/15 (20.00%) 
Painful defaecation  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Proctalgia  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  2/15 (13.33%) 
Proctitis  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Rectal ulcer  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Short-bowel syndrome  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Varices oesophageal  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Vomiting  1  3/53 (5.66%)  7/57 (12.28%)  4/20 (20.00%)  0/6 (0.00%)  3/15 (20.00%) 
General disorders           
Asthenia  1  5/53 (9.43%)  6/57 (10.53%)  4/20 (20.00%)  1/6 (16.67%)  1/15 (6.67%) 
Chest pain  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  2/15 (13.33%) 
Chills  1  0/53 (0.00%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Fatigue  1  11/53 (20.75%)  8/57 (14.04%)  6/20 (30.00%)  1/6 (16.67%)  3/15 (20.00%) 
General physical health deterioration  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Injection site pain  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Localised oedema  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Malaise  1  0/53 (0.00%)  4/57 (7.02%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Oedema peripheral  1  9/53 (16.98%)  5/57 (8.77%)  5/20 (25.00%)  0/6 (0.00%)  3/15 (20.00%) 
Pain  1  1/53 (1.89%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Pyrexia  1  0/53 (0.00%)  2/57 (3.51%)  4/20 (20.00%)  1/6 (16.67%)  2/15 (13.33%) 
Hepatobiliary disorders           
Biliary dilatation  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cholelithiasis  1  4/53 (7.55%)  4/57 (7.02%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hyperbilirubinaemia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Jaundice  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Immune system disorders           
Hypersensitivity  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Infections and infestations           
Biliary tract infection  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Bronchitis  1  2/53 (3.77%)  1/57 (1.75%)  1/20 (5.00%)  1/6 (16.67%)  1/15 (6.67%) 
Candidiasis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Clostridium difficile colitis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cystitis  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Ear infection  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Fungal infection  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gastroenteritis  1  0/53 (0.00%)  2/57 (3.51%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Gastrointestinal bacterial infection  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Incision site infection  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Infection  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Nasopharyngitis  1  2/53 (3.77%)  5/57 (8.77%)  0/20 (0.00%)  1/6 (16.67%)  1/15 (6.67%) 
Sinusitis  1  1/53 (1.89%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Tooth abscess  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Tooth infection  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Upper respiratory tract infection  1  3/53 (5.66%)  3/57 (5.26%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Urinary tract infection  1  2/53 (3.77%)  2/57 (3.51%)  0/20 (0.00%)  1/6 (16.67%)  2/15 (13.33%) 
Viral infection  1  0/53 (0.00%)  0/57 (0.00%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Injury, poisoning and procedural complications           
Accidental overdose  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Concussion  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Humerus fracture  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Procedural pain  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Rib fracture  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Thermal burn  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Tooth fracture  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  1/53 (1.89%)  3/57 (5.26%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Albumin urine present  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Aspartate aminotransferase increased  1  2/53 (3.77%)  3/57 (5.26%)  2/20 (10.00%)  0/6 (0.00%)  2/15 (13.33%) 
Bilirubin conjugated increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Blood alkaline phosphatase increased  1  2/53 (3.77%)  5/57 (8.77%)  2/20 (10.00%)  0/6 (0.00%)  2/15 (13.33%) 
Blood bilirubin increased  1  2/53 (3.77%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood calcium increased  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Blood creatine phosphokinase increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Blood creatinine increased  1  3/53 (5.66%)  3/57 (5.26%)  2/20 (10.00%)  0/6 (0.00%)  1/15 (6.67%) 
Blood glucose increased  1  3/53 (5.66%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood lactate dehydrogenase increased  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Blood magnesium decreased  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood testosterone decreased  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood triglycerides increased  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  2/15 (13.33%) 
Blood urea increased  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Blood urine present  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Gamma-glutamyltransferase increased  1  0/53 (0.00%)  3/57 (5.26%)  2/20 (10.00%)  0/6 (0.00%)  2/15 (13.33%) 
Glycosylated haemoglobin increased  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Haematocrit increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Haemoglobin decreased  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Haemoglobin increased  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Red blood cell count increased  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Weight decreased  1  8/53 (15.09%)  4/57 (7.02%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders           
Acidosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Decreased appetite  1  2/53 (3.77%)  4/57 (7.02%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dehydration  1  1/53 (1.89%)  2/57 (3.51%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Diabetes mellitus  1  6/53 (11.32%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Glucose tolerance impaired  1  2/53 (3.77%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hyperglycaemia  1  15/53 (28.30%)  3/57 (5.26%)  7/20 (35.00%)  1/6 (16.67%)  2/15 (13.33%) 
Hypernatraemia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hyperuricaemia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Hypoglycaemia  1  2/53 (3.77%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypokalaemia  1  1/53 (1.89%)  3/57 (5.26%)  3/20 (15.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hypomagnesaemia  1  1/53 (1.89%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Hyponatraemia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Increased appetite  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Malnutrition  1  0/53 (0.00%)  3/57 (5.26%)  1/20 (5.00%)  0/6 (0.00%)  2/15 (13.33%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  2/53 (3.77%)  1/57 (1.75%)  1/20 (5.00%)  1/6 (16.67%)  0/15 (0.00%) 
Arthritis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Back pain  1  3/53 (5.66%)  3/57 (5.26%)  3/20 (15.00%)  0/6 (0.00%)  1/15 (6.67%) 
Exostosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Intervertebral disc protrusion  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Muscle spasms  1  7/53 (13.21%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  1/15 (6.67%) 
Muscular weakness  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Musculoskeletal chest pain  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Musculoskeletal pain  1  1/53 (1.89%)  4/57 (7.02%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Myalgia  1  1/53 (1.89%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Neck pain  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Pain in extremity  1  4/53 (7.55%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  2/15 (13.33%) 
Spinal osteoarthritis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Uterine leiomyoma  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Nervous system disorders           
Aphasia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Aphonia  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Cervicobrachial syndrome  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Cognitive disorder  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dizziness  1  5/53 (9.43%)  1/57 (1.75%)  4/20 (20.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dysaesthesia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Dysgeusia  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Headache  1  7/53 (13.21%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypoaesthesia  1  0/53 (0.00%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Lethargy  1  3/53 (5.66%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Loss of consciousness  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Migraine  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Muscle contractions involuntary  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Neuralgia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Peripheral sensory neuropathy  1  1/53 (1.89%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Sciatica  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Syncope  1  0/53 (0.00%)  2/57 (3.51%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Tremor  1  0/53 (0.00%)  0/57 (0.00%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Psychiatric disorders           
Agitation  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Anxiety  1  3/53 (5.66%)  3/57 (5.26%)  2/20 (10.00%)  0/6 (0.00%)  1/15 (6.67%) 
Confusional state  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Depression  1  3/53 (5.66%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  1/15 (6.67%) 
Insomnia  1  1/53 (1.89%)  3/57 (5.26%)  0/20 (0.00%)  0/6 (0.00%)  3/15 (20.00%) 
Libido decreased  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Renal and urinary disorders           
Dysuria  1  0/53 (0.00%)  2/57 (3.51%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Glycosuria  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Haematuria  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Micturition urgency  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Pollakiuria  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  1/6 (16.67%)  0/15 (0.00%) 
Proteinuria  1  2/53 (3.77%)  1/57 (1.75%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Reproductive system and breast disorders           
Benign prostatic hyperplasia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  1/53 (1.89%)  2/57 (3.51%)  1/20 (5.00%)  1/6 (16.67%)  1/15 (6.67%) 
Dysphonia  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Dyspnoea  1  5/53 (9.43%)  3/57 (5.26%)  2/20 (10.00%)  0/6 (0.00%)  2/15 (13.33%) 
Hypoxia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Nasal dryness  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Painful respiration  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Pleural effusion  1  0/53 (0.00%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  0/15 (0.00%) 
Reflux laryngitis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Rhinitis allergic  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Rhinorrhoea  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Sinus congestion  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Throat tightness  1  1/53 (1.89%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Skin and subcutaneous tissue disorders           
Alopecia  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Dry skin  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Eczema  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Exfoliative rash  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hyperhidrosis  1  0/53 (0.00%)  3/57 (5.26%)  1/20 (5.00%)  1/6 (16.67%)  1/15 (6.67%) 
Night sweats  1  3/53 (5.66%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Rash  1  4/53 (7.55%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  2/15 (13.33%) 
Skin exfoliation  1  1/53 (1.89%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Skin hyperpigmentation  1  0/53 (0.00%)  0/57 (0.00%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Skin lesion  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Skin ulcer  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Social circumstances           
Alcohol use  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Vascular disorders           
Axillary vein thrombosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Flushing  1  5/53 (9.43%)  4/57 (7.02%)  0/20 (0.00%)  0/6 (0.00%)  2/15 (13.33%) 
Hypertension  1  3/53 (5.66%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  0/15 (0.00%) 
Hypotension  1  1/53 (1.89%)  1/57 (1.75%)  2/20 (10.00%)  0/6 (0.00%)  1/15 (6.67%) 
Lymphoedema  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Orthostatic hypotension  1  0/53 (0.00%)  1/57 (1.75%)  0/20 (0.00%)  0/6 (0.00%)  1/15 (6.67%) 
Subclavian vein thrombosis  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
Thrombophlebitis superficial  1  0/53 (0.00%)  0/57 (0.00%)  1/20 (5.00%)  0/6 (0.00%)  0/15 (0.00%) 
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.
Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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 pooled data (i.e.,data from all sites) in clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00690430     History of Changes
Other Study ID Numbers: CSOM230C2303
2007-000739-25 ( EudraCT Number )
First Submitted: May 15, 2008
First Posted: June 4, 2008
Results First Submitted: April 5, 2013
Results First Posted: July 30, 2013
Last Update Posted: July 30, 2013