Trial Outcomes & Findings for Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease (NCT NCT00690430)
NCT ID: NCT00690430
Last Updated: 2013-07-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
186 participants
Primary outcome timeframe
Month 6
Results posted on
2013-07-30
Participant Flow
186 patients were screened and 110 were randomized into the study.
Participant milestones
| Measure |
Pasireotide LAR
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.
|
Octreotide LAR
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.
|
Extension: Octreotide LAR/Pasireotide LAR
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.
|
|---|---|---|---|
|
Core Phase
STARTED
|
53
|
57
|
0
|
|
Core Phase
COMPLETED
|
35
|
34
|
0
|
|
Core Phase
NOT COMPLETED
|
18
|
23
|
0
|
|
Extension Phase
STARTED
|
20
|
6
|
15
|
|
Extension Phase
COMPLETED
|
2
|
1
|
2
|
|
Extension Phase
NOT COMPLETED
|
18
|
5
|
13
|
Reasons for withdrawal
| Measure |
Pasireotide LAR
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.
|
Octreotide LAR
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.
|
Extension: Octreotide LAR/Pasireotide LAR
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.
|
|---|---|---|---|
|
Core Phase
Abnormal Laboratory value
|
0
|
1
|
0
|
|
Core Phase
Adverse Event
|
5
|
1
|
0
|
|
Core Phase
Death
|
0
|
2
|
0
|
|
Core Phase
Protocol Violation
|
1
|
0
|
0
|
|
Core Phase
Withdrawal by Subject
|
3
|
3
|
0
|
|
Core Phase
Subject no longer requires study drug
|
1
|
0
|
0
|
|
Core Phase
Lack of Efficacy
|
8
|
10
|
0
|
|
Core Phase
Administrative Problems
|
0
|
1
|
0
|
|
Core Phase
Early Termination
|
0
|
5
|
0
|
|
Extension Phase
Lack of Efficacy
|
3
|
1
|
4
|
|
Extension Phase
Abnormal Lab Values
|
1
|
0
|
0
|
|
Extension Phase
Abnormal test procedure results
|
1
|
0
|
0
|
|
Extension Phase
Administrative Problems
|
0
|
1
|
1
|
|
Extension Phase
Adverse Event
|
2
|
1
|
2
|
|
Extension Phase
Death
|
1
|
1
|
1
|
|
Extension Phase
Withdrawal by Subject
|
0
|
0
|
2
|
|
Extension Phase
Early Termination
|
10
|
1
|
3
|
Baseline Characteristics
Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease
Baseline characteristics by cohort
| Measure |
Pasireotide LAR
n=53 Participants
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.
|
Octreotide LAR
n=57 Participants
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
n=110 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
61.2 Years
STANDARD_DEVIATION 9.21 • n=99 Participants
|
62.8 Years
STANDARD_DEVIATION 11.91 • n=107 Participants
|
62 Years
STANDARD_DEVIATION 10.67 • n=206 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
47 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=99 Participants
|
34 Participants
n=107 Participants
|
63 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Month 6Population: 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.
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.
Outcome measures
| Measure |
Pasireotide LAR
n=43 Participants
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.
|
Octreotide LAR
n=45 Participants
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.
|
|---|---|---|
|
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
Diarrhea and Flushing (N=37, 39)
|
13.5 Percentage of Participants
Interval 4.5 to 28.8
|
28.2 Percentage of Participants
Interval 15.0 to 44.9
|
|
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
Diarrhea (N=2, 5)
|
100 Percentage of Participants
Interval 15.8 to 100.0
|
20.0 Percentage of Participants
Interval 0.5 to 71.6
|
|
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
Flushing (N=4, 1)
|
50 Percentage of Participants
Interval 6.8 to 93.2
|
0.0 Percentage of Participants
Interval 0.0 to 97.5
|
|
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
Overall (N=43, 45)
|
20.9 Percentage of Participants
Interval 10.0 to 36.0
|
26.7 Percentage of Participants
Interval 14.6 to 41.9
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Pasireotide LAR
n=26 Participants
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.
|
Octreotide LAR
n=32 Participants
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.
|
|---|---|---|
|
Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.
Predominantly Diarrhea (D) (N=2, 4)
|
-44.2 Percentage of Episodes
Standard Deviation 10.26
|
-22.9 Percentage of Episodes
Standard Deviation 31.68
|
|
Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.
Diarrhea and Flushing (N=24, 28)
|
-23.5 Percentage of Episodes
Standard Deviation 24.28
|
-38.4 Percentage of Episodes
Standard Deviation 28.74
|
|
Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.
Overall (N=26, 32)
|
-25.1 Percentage of Episodes
Standard Deviation 24.04
|
-36.5 Percentage of Episodes
Standard Deviation 29.05
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Pasireotide LAR
n=28 Participants
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.
|
Octreotide LAR
n=29 Participants
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.
|
|---|---|---|
|
Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.
Diarrhea and Flushing (N=24, 28)
|
-41.0 Percentage of Episodes
Standard Deviation 41.06
|
-52.8 Percentage of Episodes
Standard Deviation 32.18
|
|
Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.
Predominately Flushing (N=4, 1)
|
-48.4 Percentage of Episodes
Standard Deviation 23.13
|
47.2 Percentage of Episodes
Standard Deviation NA
Standard Deviation could not be calculated because there was only 1 patient analyzed.
|
|
Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.
Overall (N=28, 29)
|
-42.1 Percentage of Episodes
Standard Deviation 38.76
|
-49.4 Percentage of Episodes
Standard Deviation 36.65
|
SECONDARY outcome
Timeframe: Month 6Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: 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.
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.
Outcome measures
| Measure |
Pasireotide LAR
n=51 Participants
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.
|
Octreotide LAR
n=52 Participants
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.
|
|---|---|---|
|
Objective Tumor Response Rate Assessed by Investigator
|
2.0 Percentage of Participants
Interval 0.0 to 10.4
|
3.8 Percentage of Participants
Interval 0.5 to 13.2
|
SECONDARY outcome
Timeframe: Month 6Population: 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.
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.
Outcome measures
| Measure |
Pasireotide LAR
n=51 Participants
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.
|
Octreotide LAR
n=52 Participants
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.
|
|---|---|---|
|
Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria
|
62.7 Percentage of participants
Interval 48.1 to 75.9
|
46.2 Percentage of participants
Interval 32.2 to 60.5
|
SECONDARY outcome
Timeframe: Month 6Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: 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.
Outcome measures
Outcome data not reported
Adverse Events
Pasireotide LAR
Serious events: 15 serious events
Other events: 50 other events
Deaths: 0 deaths
Octreotide LAR
Serious events: 19 serious events
Other events: 48 other events
Deaths: 0 deaths
Extension Phase Pasireotide LAR
Serious events: 9 serious events
Other events: 19 other events
Deaths: 0 deaths
Extension Phase Octreotide LAR
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Crossover to Pasireotide LAR
Serious events: 7 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pasireotide LAR
n=53 participants at risk
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.
|
Octreotide LAR
n=57 participants at risk
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.
|
Extension Phase Pasireotide LAR
n=20 participants at risk
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.
|
Extension Phase Octreotide LAR
n=6 participants at risk
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.
|
Crossover to Pasireotide LAR
n=15 participants at risk
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.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Carcinoid heart disease
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Endocardial fibrosis
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Tricuspid valve incompetence
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
3/53
|
5.3%
3/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Anorectal disorder
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Diarrhea
|
7.5%
4/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Intestinal infarction
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Vomiting
|
1.9%
1/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Asthenia
|
0.00%
0/53
|
3.5%
2/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Chest pain
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Condition aggravated
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Device dislocation
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Device infusion issue
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Fatigue
|
3.8%
2/53
|
3.5%
2/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
General disorders
General physical health deterioration
|
1.9%
1/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Localised oedema
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
General disorders
Malaise
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Medical device complication
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Oedema peripheral
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Cholecystitis
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/53
|
3.5%
2/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Hepatomegaly
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Clostridial infection
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Device related infection
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Infectious peritonitis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Alanine aminotransferase increased
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Aspartate aminotransferase increased
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood bicarbonate decreased
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood creatinine increased
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood pH increased
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Liver function test abnormal
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Troponin increased
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Weight decreased
|
3.8%
2/53
|
3.5%
2/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/53
|
3.5%
2/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
2/53
|
3.5%
2/57
|
5.0%
1/20
|
16.7%
1/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.5%
4/53
|
0.00%
0/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumour
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumour of the gastrointestinal tract
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to chest wall
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic carcinoid tumour
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Central nervous system lesion
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Nephritis
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Renal and urinary disorders
Renal failure chronic
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Urinary tract disorder
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Social circumstances
Respite care
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Flushing
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Vascular disorders
Vein disorder
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
Other adverse events
| Measure |
Pasireotide LAR
n=53 participants at risk
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.
|
Octreotide LAR
n=57 participants at risk
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.
|
Extension Phase Pasireotide LAR
n=20 participants at risk
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.
|
Extension Phase Octreotide LAR
n=6 participants at risk
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.
|
Crossover to Pasireotide LAR
n=15 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.7%
3/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Aortic valve sclerosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Bradycardia
|
3.8%
2/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Cardiac disorders
Bundle branch block right
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Dilatation ventricular
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Mitral valve incompetence
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Cardiac disorders
Palpitations
|
0.00%
0/53
|
8.8%
5/57
|
0.00%
0/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Cardiac disorders
Pulmonary valve incompetence
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Cardiac disorders
Tricuspid valve incompetence
|
3.8%
2/53
|
5.3%
3/57
|
5.0%
1/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Congenital, familial and genetic disorders
Birth mark
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/53
|
0.00%
0/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Eye disorders
Dry eye
|
3.8%
2/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Eye disorders
Eye pain
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Eye disorders
Glaucoma
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Eye disorders
Visual impairment
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal distension
|
5.7%
3/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal pain
|
15.1%
8/53
|
14.0%
8/57
|
5.0%
1/20
|
0.00%
0/6
|
20.0%
3/15
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
2/53
|
5.3%
3/57
|
10.0%
2/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/53
|
7.0%
4/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Diarrhoea
|
22.6%
12/53
|
15.8%
9/57
|
20.0%
4/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Gastrointestinal disorders
Dry mouth
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dyspepsia
|
5.7%
3/53
|
5.3%
3/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/53
|
0.00%
0/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Faecal incontinence
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Flatulence
|
13.2%
7/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/53
|
1.8%
1/57
|
15.0%
3/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.9%
1/53
|
3.5%
2/57
|
20.0%
4/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Nausea
|
18.9%
10/53
|
12.3%
7/57
|
20.0%
4/20
|
0.00%
0/6
|
20.0%
3/15
|
|
Gastrointestinal disorders
Painful defaecation
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Proctalgia
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Gastrointestinal disorders
Proctitis
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Gastrointestinal disorders
Rectal ulcer
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Short-bowel syndrome
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
3/53
|
12.3%
7/57
|
20.0%
4/20
|
0.00%
0/6
|
20.0%
3/15
|
|
General disorders
Asthenia
|
9.4%
5/53
|
10.5%
6/57
|
20.0%
4/20
|
16.7%
1/6
|
6.7%
1/15
|
|
General disorders
Chest pain
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
13.3%
2/15
|
|
General disorders
Chills
|
0.00%
0/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Fatigue
|
20.8%
11/53
|
14.0%
8/57
|
30.0%
6/20
|
16.7%
1/6
|
20.0%
3/15
|
|
General disorders
General physical health deterioration
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Injection site pain
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
General disorders
Localised oedema
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Malaise
|
0.00%
0/53
|
7.0%
4/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Oedema peripheral
|
17.0%
9/53
|
8.8%
5/57
|
25.0%
5/20
|
0.00%
0/6
|
20.0%
3/15
|
|
General disorders
Pain
|
1.9%
1/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
General disorders
Pyrexia
|
0.00%
0/53
|
3.5%
2/57
|
20.0%
4/20
|
16.7%
1/6
|
13.3%
2/15
|
|
Hepatobiliary disorders
Biliary dilatation
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Cholelithiasis
|
7.5%
4/53
|
7.0%
4/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Infections and infestations
Biliary tract infection
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Bronchitis
|
3.8%
2/53
|
1.8%
1/57
|
5.0%
1/20
|
16.7%
1/6
|
6.7%
1/15
|
|
Infections and infestations
Candidiasis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Cystitis
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Ear infection
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Fungal infection
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/53
|
3.5%
2/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Gastrointestinal bacterial infection
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Incision site infection
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Infection
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
2/53
|
8.8%
5/57
|
0.00%
0/20
|
16.7%
1/6
|
6.7%
1/15
|
|
Infections and infestations
Sinusitis
|
1.9%
1/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Tooth infection
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Upper respiratory tract infection
|
5.7%
3/53
|
5.3%
3/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Infections and infestations
Urinary tract infection
|
3.8%
2/53
|
3.5%
2/57
|
0.00%
0/20
|
16.7%
1/6
|
13.3%
2/15
|
|
Infections and infestations
Viral infection
|
0.00%
0/53
|
0.00%
0/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Alanine aminotransferase increased
|
1.9%
1/53
|
5.3%
3/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Albumin urine present
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Aspartate aminotransferase increased
|
3.8%
2/53
|
5.3%
3/57
|
10.0%
2/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Investigations
Bilirubin conjugated increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Blood alkaline phosphatase increased
|
3.8%
2/53
|
8.8%
5/57
|
10.0%
2/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Investigations
Blood bilirubin increased
|
3.8%
2/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood calcium increased
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Blood creatinine increased
|
5.7%
3/53
|
5.3%
3/57
|
10.0%
2/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Blood glucose increased
|
5.7%
3/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Blood magnesium decreased
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood testosterone decreased
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood triglycerides increased
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Investigations
Blood urea increased
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Blood urine present
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/53
|
5.3%
3/57
|
10.0%
2/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Investigations
Glycosylated haemoglobin increased
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Haematocrit increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Haemoglobin decreased
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Haemoglobin increased
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Red blood cell count increased
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Investigations
Weight decreased
|
15.1%
8/53
|
7.0%
4/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.8%
2/53
|
7.0%
4/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Dehydration
|
1.9%
1/53
|
3.5%
2/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
11.3%
6/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Glucose tolerance impaired
|
3.8%
2/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
28.3%
15/53
|
5.3%
3/57
|
35.0%
7/20
|
16.7%
1/6
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
3.8%
2/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.9%
1/53
|
5.3%
3/57
|
15.0%
3/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.9%
1/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Increased appetite
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/53
|
5.3%
3/57
|
5.0%
1/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
2/53
|
1.8%
1/57
|
5.0%
1/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
3/53
|
5.3%
3/57
|
15.0%
3/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
13.2%
7/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.9%
1/53
|
7.0%
4/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.9%
1/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.5%
4/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Aphasia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Aphonia
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Cervicobrachial syndrome
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Dizziness
|
9.4%
5/53
|
1.8%
1/57
|
20.0%
4/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Headache
|
13.2%
7/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Lethargy
|
5.7%
3/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Migraine
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Muscle contractions involuntary
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
1.9%
1/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Nervous system disorders
Sciatica
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Syncope
|
0.00%
0/53
|
3.5%
2/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Nervous system disorders
Tremor
|
0.00%
0/53
|
0.00%
0/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Psychiatric disorders
Agitation
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Psychiatric disorders
Anxiety
|
5.7%
3/53
|
5.3%
3/57
|
10.0%
2/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Psychiatric disorders
Confusional state
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Psychiatric disorders
Depression
|
5.7%
3/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Psychiatric disorders
Insomnia
|
1.9%
1/53
|
5.3%
3/57
|
0.00%
0/20
|
0.00%
0/6
|
20.0%
3/15
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/53
|
3.5%
2/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Glycosuria
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Pollakiuria
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
16.7%
1/6
|
0.00%
0/15
|
|
Renal and urinary disorders
Proteinuria
|
3.8%
2/53
|
1.8%
1/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.9%
1/53
|
3.5%
2/57
|
5.0%
1/20
|
16.7%
1/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.4%
5/53
|
5.3%
3/57
|
10.0%
2/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Painful respiration
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Reflux laryngitis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Throat tightness
|
1.9%
1/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/53
|
5.3%
3/57
|
5.0%
1/20
|
16.7%
1/6
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.7%
3/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.5%
4/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
1.9%
1/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/53
|
0.00%
0/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Social circumstances
Alcohol use
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Axillary vein thrombosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Flushing
|
9.4%
5/53
|
7.0%
4/57
|
0.00%
0/20
|
0.00%
0/6
|
13.3%
2/15
|
|
Vascular disorders
Hypertension
|
5.7%
3/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Hypotension
|
1.9%
1/53
|
1.8%
1/57
|
10.0%
2/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/53
|
1.8%
1/57
|
0.00%
0/20
|
0.00%
0/6
|
6.7%
1/15
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/53
|
0.00%
0/57
|
5.0%
1/20
|
0.00%
0/6
|
0.00%
0/15
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER