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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00690430
• Collaborator: (none)
• Enrollment: 186
• Locations: 62
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this randomized, multicenter, Phase III study was to compare the efficacy of paseriotide LAR and octreotide LAR in patients whose disease-related symptoms are inadequately controlled by currently available somatostatin analogues.

Condition or Disease	Intervention/Treatment	Phase
Symptomatic Refractory Resistant Carcinoid Disease	Drug: Pasireotide; Drug: Octreotide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Blinded Efficacy and Safety Study of Pasireotide LAR vs Octreotide LAR in Patients With Metastatic Carcinoid Tumors Whose Disease-related Symptoms Are Inadequately Controlled by Somatostatin Analogues.
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Pasireotide; Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed; Other Names: SOM230
Active Comparator: 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.	Drug: Octreotide; Octreotide LAR 40mg i.m. depot injection - Patients may also receive octreotide 100 µg s.c. 3 times a day for symptom control as needed; Other Names: Sadostatin LAR

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment. [Month 6]

   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.

Secondary Outcome Measures

1. Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment. [6 months]

   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.

2. Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment. [6 months]

   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.

3. Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response. [Month 6]

4. Objective Tumor Response Rate Assessed by Investigator [Month 6]

   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.

5. Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria [Month 6]

   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.

6. Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire [Month 6]

7. Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression [Month 6]

8. Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response [Month 6]

9. Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements [Month 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male or female patients aged 18 or greater

• Patients with carcinoid tumors and symptoms (diarrhea and flushing) that are not adequately controlled by somatostatin analogues.

• Female patients of child bearing potential must have a negative pregnancy test at baseline.

• Patients for whom written informed consent to participate in the study has been obtained.

Exclusion criteria:

• Patients receiving radiolabeled somatostatin analogue therapy within the 3 months or any cytotoxic chemotherapy or interferon therapy within the 4 weeks prior to randomization

• Diabetic patients on anti-diabetic medications whose fasting blood glucose is poorly controlled as indicated by HBA1C > 8%

• Patients with symptomatic cholelithiasis

• Patient with malabsorption syndrome, short bowel or cholegenic diarrhea not controlled by specific therapeutic means.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scottsdale Healthcare/TGen Clinical Research Service TGen Clinical Research Service	Scottsdale	Arizona	United States	85258
2	University of Arizona / Arizona Cancer Center	Tucson	Arizona	United States	85724
3	Loma Linda University Dept. of Loma Linda CancerCent	Loma Linda	California	United States	92354
4	Cedars Sinai Medical Center Cedars Sinai 4	Los Angeles	California	United States	90048
5	H. Lee Moffitt Cancer Center/University of South Florida Dept of H. Lee Moffit	Tampa	Florida	United States	33612
6	Montefiore Medical Center MMC	Bronx	New York	United States	10467
7	Mount Sinai School of Medicine Study Coordinator	New York	New York	United States	10029
8	Duke University Medical Center Dept. of Duke Cancer Center(2)	Durham	North Carolina	United States	27710
9	St. Luke's Hospital and Health Network St. Luke's Cancer Network	Bethlehem	Pennsylvania	United States
10	MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (9)	Houston	Texas	United States	77030-4009
11	Novartis Investigative Site	Buenos Aires		Argentina	C1264AAA
12	Novartis Investigative Site	Buenos Aires		Argentina	C1426ANZ
13	Novartis Investigative Site	Graz		Austria	8036
14	Novartis Investigative Site	Salzburg		Austria	5020
15	Novartis Investigative Site	Vienna		Austria	A-1090
16	Novartis Investigative Site	Bruxelles		Belgium	1200
17	Novartis Investigative Site	Gent		Belgium	9000
18	Novartis Investigative Site	Fortaleza	CE	Brazil	60430-370
19	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 2T9
20	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 2Y9
21	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 1A1
22	Novartis Investigative Site	Clichy		France	92110
23	Novartis Investigative Site	Dijon		France	21079
24	Novartis Investigative Site	Lyon		France	69437
25	Novartis Investigative Site	Marseille cedex 05		France	13385
26	Novartis Investigative Site	Montpellier cedex 5		France	34295
27	Novartis Investigative Site	Nice Cedex		France	06202
28	Novartis Investigative Site	Strasbourg		France	67098
29	Novartis Investigative Site	Bad Berka		Germany	99438
30	Novartis Investigative Site	Berlin		Germany	12200
31	Novartis Investigative Site	Berlin		Germany	13353
32	Novartis Investigative Site	Heidelberg		Germany	69120
33	Novartis Investigative Site	Mainz		Germany	D-55101
34	Novartis Investigative Site	München		Germany	80336
35	Novartis Investigative Site	Jerusalem		Israel	91120
36	Novartis Investigative Site	Bologna	BO	Italy	40138
37	Novartis Investigative Site	Milano	MI	Italy	20132
38	Novartis Investigative Site	Milano	MI	Italy	20141
39	Novartis Investigative Site	Milano	MI	Italy	20162
40	Novartis Investigative Site	Modena	MO	Italy	41100
41	Novartis Investigative Site	Perugia	PG	Italy	06100
42	Novartis Investigative Site	Roma	RM	Italy	00168
43	Novartis Investigative Site	Orbassano	TO	Italy	10043
44	Novartis Investigative Site	Tromsø		Norway	9038
45	Novartis Investigative Site	Trondheim		Norway	N-7006
46	Novartis Investigative Site	Gliwice	Slaskie	Poland	44-101
47	Novartis Investigative Site	Gdansk		Poland	80-958
48	Novartis Investigative Site	Singapore		Singapore	169610
49	Novartis Investigative Site	Hospitalet de Llobregat	Cataluña	Spain	08907
50	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
51	Novartis Investigative Site	Jönköping		Sweden	SE-551 85
52	Novartis Investigative Site	Linköping		Sweden	SE-581 85
53	Novartis Investigative Site	Lund		Sweden	SE-221 85
54	Novartis Investigative Site	Stockholm		Sweden	SE-141 86
55	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
56	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
57	Novartis Investigative Site	Withington	Greater Manchester	United Kingdom	M20 4BX
58	Novartis Investigative Site	Sheffield	South Yorkshire	United Kingdom	S10 2JF
59	Novartis Investigative Site	Basingstoke		United Kingdom	RG24 9NA
60	Novartis Investigative Site	Birmingham		United Kingdom	B15 2TH
61	Novartis Investigative Site	Glasgow		United Kingdom	G12 0YN
62	Novartis Investigative Site	London		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.
• Related Info

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00690430
• Other Study ID Numbers: CSOM230C2303; 2007-000739-25
• First Posted: Jun 4, 2008
• Last Update Posted: Jul 30, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Novartis Pharmaceuticals: Carcinoid; neuroendocrine; gastroenteropancreatic; somatostatin analogue; Symptomatic Refractory Resistant Carcinoid Disease
• Additional relevant MeSH terms: Carcinoid Tumor; Octreotide; Pasireotide

Study Results

Participant Flow

Recruitment Details	186 patients were screened and 110 were randomized into the study.

Arm/Group Title	Pasireotide LAR	Octreotide LAR	Extension: Octreotide LAR/Pasireotide LAR
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	57	0
COMPLETED	35	34	0
NOT COMPLETED	18	23	0
Period Title: Core Phase
STARTED	20	6	15
COMPLETED	2	1	2
NOT COMPLETED	18	5	13

Baseline Characteristics

Arm/Group Title	Pasireotide LAR	Octreotide LAR	Total
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 Participants	53	57	110
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.2 (9.21)	62.8 (11.91)	62 (10.67)
Sex: Female, Male (Count of Participants)
Female	24 45.3%	23 40.4%	47 42.7%
Male	29 54.7%	34 59.6%	63 57.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.
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

Outcome Measure Data

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
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.
Measure Participants	43	45
Diarrhea and Flushing (N=37, 39)	13.5 25.5%	28.2 49.5%
Diarrhea (N=2, 5)	100 188.7%	20.0 35.1%
Flushing (N=4, 1)	50 94.3%	0.0 0%
Overall (N=43, 45)	20.9 39.4%	26.7 46.8%

2. Secondary Outcome

Title	Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.
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

Outcome Measure Data

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
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.
Measure Participants	26	32
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.
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

Outcome Measure Data

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
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.
Measure Participants	28	29
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 (NA)
Overall (N=28, 29)	-42.1 (38.76)	-49.4 (36.65)

4. Secondary Outcome

Title	Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.
Time Frame	Month 6

Outcome Measure Data

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
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.
Measure Participants	0	0

5. Secondary Outcome

Title	Objective Tumor Response Rate Assessed by Investigator
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

Outcome Measure Data

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
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.
Measure Participants	51	52
Number (95% Confidence Interval) [Percentage of Participants]	2.0 3.8%	3.8 6.7%

6. Secondary Outcome

Title	Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria
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

Outcome Measure Data

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
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.
Measure Participants	51	52
Number (95% Confidence Interval) [Percentage of participants]	62.7 118.3%	46.2 81.1%

7. Secondary Outcome

Title	Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire
Time Frame	Month 6

Outcome Measure Data

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
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.
Measure Participants	0	0

8. Secondary Outcome

Title	Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression
Time Frame	Month 6

Outcome Measure Data

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
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.
Measure Participants	0	0

9. Secondary Outcome

Title	Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response
Time Frame	Month 6

Outcome Measure Data

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
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.
Measure Participants	0	0

10. Secondary Outcome

Title	Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements
Time Frame	Month 6

Outcome Measure Data

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
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.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Pasireotide LAR		Octreotide LAR		Extension Phase Pasireotide LAR		Extension Phase Octreotide LAR		Crossover to Pasireotide LAR
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pasireotide LAR		Octreotide LAR		Extension Phase Pasireotide LAR		Extension Phase Octreotide LAR		Crossover to Pasireotide LAR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/53 (28.3%)		19/57 (33.3%)		9/20 (45%)		2/6 (33.3%)		7/15 (46.7%)
Cardiac disorders
Carcinoid heart disease	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Cardiac failure	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Cardiomyopathy	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Endocardial fibrosis	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Sinus bradycardia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Tricuspid valve incompetence	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Gastrointestinal disorders
Abdominal pain	3/53 (5.7%)		3/57 (5.3%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Anorectal disorder	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Colitis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Diarrhea	4/53 (7.5%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Ileus	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Intestinal infarction	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Intestinal perforation	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Mesenteric vein thrombosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Nausea	0/53 (0%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Oesophageal varices haemorrhage	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Pneumoperitoneum	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Vomiting	1/53 (1.9%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
General disorders
Asthenia	0/53 (0%)		2/57 (3.5%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Chest pain	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Condition aggravated	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Device dislocation	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Device infusion issue	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Fatigue	2/53 (3.8%)		2/57 (3.5%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
General physical health deterioration	1/53 (1.9%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Localised oedema	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Malaise	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Medical device complication	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Oedema peripheral	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Hepatobiliary disorders
Cholangitis	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Cholecystitis	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Cholestasis	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hepatic failure	0/53 (0%)		2/57 (3.5%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Hepatomegaly	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Infections and infestations
Clostridial infection	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Device related infection	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Infectious peritonitis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Urinary tract infection	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Procedural pain	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Tendon rupture	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Investigations
Alanine aminotransferase increased	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Aspartate aminotransferase increased	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Blood alkaline phosphatase increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Blood bicarbonate decreased	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Blood creatinine increased	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Blood pH increased	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Gamma-glutamyltransferase increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hepatic enzyme increased	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Liver function test abnormal	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Troponin increased	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Weight decreased	2/53 (3.8%)		2/57 (3.5%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/53 (0%)		2/57 (3.5%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Dehydration	2/53 (3.8%)		2/57 (3.5%)		1/20 (5%)		1/6 (16.7%)		1/15 (6.7%)
Diabetes mellitus	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Hyperglycaemia	4/53 (7.5%)		0/57 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Hyperkalaemia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hypoglycaemia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hypokalaemia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hyponatraemia	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Hypovolaemia	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Malnutrition	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Metabolic acidosis	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Type 2 diabetes mellitus	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Intervertebral disc disorder	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Pain in extremity	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumour	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Carcinoid tumour of the gastrointestinal tract	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Metastases to chest wall	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Metastatic carcinoid tumour	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Neoplasm malignant	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Nervous system disorders
Central nervous system lesion	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hemiparesis	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Psychiatric disorders
Confusional state	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Renal and urinary disorders
Nephritis	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Renal failure	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Renal failure acute	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Renal failure chronic	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Urinary tract disorder	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Pulmonary embolism	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Social circumstances
Respite care	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Vascular disorders
Flushing	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Orthostatic hypotension	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Vein disorder	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Pasireotide LAR		Octreotide LAR		Extension Phase Pasireotide LAR		Extension Phase Octreotide LAR		Crossover to Pasireotide LAR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/53 (94.3%)		48/57 (84.2%)		19/20 (95%)		5/6 (83.3%)		12/15 (80%)
Blood and lymphatic system disorders
Anaemia	3/53 (5.7%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Leukocytosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Cardiac disorders
Aortic valve sclerosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Atrial fibrillation	0/53 (0%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Bradycardia	2/53 (3.8%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Bundle branch block right	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Coronary artery disease	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dilatation ventricular	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Mitral valve incompetence	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Palpitations	0/53 (0%)		5/57 (8.8%)		0/20 (0%)		0/6 (0%)		2/15 (13.3%)
Pulmonary valve incompetence	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Tricuspid valve incompetence	2/53 (3.8%)		3/57 (5.3%)		1/20 (5%)		0/6 (0%)		2/15 (13.3%)
Congenital, familial and genetic disorders
Birth mark	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Endocrine disorders
Hypothyroidism	0/53 (0%)		0/57 (0%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Eye disorders
Conjunctivitis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dry eye	2/53 (3.8%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Eye pain	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Glaucoma	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Visual impairment	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Gastrointestinal disorders
Abdominal distension	3/53 (5.7%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Abdominal pain	8/53 (15.1%)		8/57 (14%)		1/20 (5%)		0/6 (0%)		3/15 (20%)
Abdominal pain lower	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Abdominal pain upper	2/53 (3.8%)		3/57 (5.3%)		2/20 (10%)		1/6 (16.7%)		0/15 (0%)
Anal fissure	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Anal haemorrhage	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Constipation	0/53 (0%)		4/57 (7%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Diarrhoea	12/53 (22.6%)		9/57 (15.8%)		4/20 (20%)		0/6 (0%)		2/15 (13.3%)
Dry mouth	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Duodenal ulcer	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dyspepsia	3/53 (5.7%)		3/57 (5.3%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Dysphagia	0/53 (0%)		0/57 (0%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Faecal incontinence	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Flatulence	7/53 (13.2%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Gastritis	0/53 (0%)		1/57 (1.8%)		3/20 (15%)		0/6 (0%)		1/15 (6.7%)
Gastrointestinal haemorrhage	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Haematochezia	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Haemorrhoids	1/53 (1.9%)		2/57 (3.5%)		4/20 (20%)		0/6 (0%)		0/15 (0%)
Nausea	10/53 (18.9%)		7/57 (12.3%)		4/20 (20%)		0/6 (0%)		3/15 (20%)
Painful defaecation	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Proctalgia	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		2/15 (13.3%)
Proctitis	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Rectal ulcer	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Short-bowel syndrome	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Varices oesophageal	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Vomiting	3/53 (5.7%)		7/57 (12.3%)		4/20 (20%)		0/6 (0%)		3/15 (20%)
General disorders
Asthenia	5/53 (9.4%)		6/57 (10.5%)		4/20 (20%)		1/6 (16.7%)		1/15 (6.7%)
Chest pain	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		2/15 (13.3%)
Chills	0/53 (0%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Fatigue	11/53 (20.8%)		8/57 (14%)		6/20 (30%)		1/6 (16.7%)		3/15 (20%)
General physical health deterioration	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Injection site pain	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Localised oedema	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Malaise	0/53 (0%)		4/57 (7%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Oedema peripheral	9/53 (17%)		5/57 (8.8%)		5/20 (25%)		0/6 (0%)		3/15 (20%)
Pain	1/53 (1.9%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Pyrexia	0/53 (0%)		2/57 (3.5%)		4/20 (20%)		1/6 (16.7%)		2/15 (13.3%)
Hepatobiliary disorders
Biliary dilatation	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Cholelithiasis	4/53 (7.5%)		4/57 (7%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Hyperbilirubinaemia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Jaundice	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Immune system disorders
Hypersensitivity	0/53 (0%)		0/57 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Infections and infestations
Biliary tract infection	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Bronchitis	2/53 (3.8%)		1/57 (1.8%)		1/20 (5%)		1/6 (16.7%)		1/15 (6.7%)
Candidiasis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Clostridium difficile colitis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Cystitis	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Ear infection	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Fungal infection	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Gastroenteritis	0/53 (0%)		2/57 (3.5%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Gastrointestinal bacterial infection	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Incision site infection	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Infection	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Nasopharyngitis	2/53 (3.8%)		5/57 (8.8%)		0/20 (0%)		1/6 (16.7%)		1/15 (6.7%)
Sinusitis	1/53 (1.9%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Tooth abscess	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Tooth infection	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Upper respiratory tract infection	3/53 (5.7%)		3/57 (5.3%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Urinary tract infection	2/53 (3.8%)		2/57 (3.5%)		0/20 (0%)		1/6 (16.7%)		2/15 (13.3%)
Viral infection	0/53 (0%)		0/57 (0%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Concussion	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Humerus fracture	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Procedural pain	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Rib fracture	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Thermal burn	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Tooth fracture	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Investigations
Alanine aminotransferase increased	1/53 (1.9%)		3/57 (5.3%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Albumin urine present	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Aspartate aminotransferase increased	2/53 (3.8%)		3/57 (5.3%)		2/20 (10%)		0/6 (0%)		2/15 (13.3%)
Bilirubin conjugated increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Blood alkaline phosphatase increased	2/53 (3.8%)		5/57 (8.8%)		2/20 (10%)		0/6 (0%)		2/15 (13.3%)
Blood bilirubin increased	2/53 (3.8%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Blood calcium increased	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Blood creatine phosphokinase increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Blood creatinine increased	3/53 (5.7%)		3/57 (5.3%)		2/20 (10%)		0/6 (0%)		1/15 (6.7%)
Blood glucose increased	3/53 (5.7%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Blood lactate dehydrogenase increased	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Blood magnesium decreased	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Blood testosterone decreased	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Blood triglycerides increased	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		2/15 (13.3%)
Blood urea increased	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Blood urine present	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Gamma-glutamyltransferase increased	0/53 (0%)		3/57 (5.3%)		2/20 (10%)		0/6 (0%)		2/15 (13.3%)
Glycosylated haemoglobin increased	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Haematocrit increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Haemoglobin decreased	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Haemoglobin increased	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Red blood cell count increased	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Weight decreased	8/53 (15.1%)		4/57 (7%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Metabolism and nutrition disorders
Acidosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Decreased appetite	2/53 (3.8%)		4/57 (7%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dehydration	1/53 (1.9%)		2/57 (3.5%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Diabetes mellitus	6/53 (11.3%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Glucose tolerance impaired	2/53 (3.8%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		1/15 (6.7%)
Hyperglycaemia	15/53 (28.3%)		3/57 (5.3%)		7/20 (35%)		1/6 (16.7%)		2/15 (13.3%)
Hypernatraemia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Hyperuricaemia	0/53 (0%)		0/57 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Hypoglycaemia	2/53 (3.8%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Hypokalaemia	1/53 (1.9%)		3/57 (5.3%)		3/20 (15%)		0/6 (0%)		1/15 (6.7%)
Hypomagnesaemia	1/53 (1.9%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Hyponatraemia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Increased appetite	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Malnutrition	0/53 (0%)		3/57 (5.3%)		1/20 (5%)		0/6 (0%)		2/15 (13.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/53 (3.8%)		1/57 (1.8%)		1/20 (5%)		1/6 (16.7%)		0/15 (0%)
Arthritis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Back pain	3/53 (5.7%)		3/57 (5.3%)		3/20 (15%)		0/6 (0%)		1/15 (6.7%)
Exostosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Intervertebral disc protrusion	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Muscle spasms	7/53 (13.2%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		1/15 (6.7%)
Muscular weakness	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Musculoskeletal chest pain	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Musculoskeletal pain	1/53 (1.9%)		4/57 (7%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Myalgia	1/53 (1.9%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Neck pain	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Pain in extremity	4/53 (7.5%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		2/15 (13.3%)
Spinal osteoarthritis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Nervous system disorders
Aphasia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Aphonia	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Cervicobrachial syndrome	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Cognitive disorder	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dizziness	5/53 (9.4%)		1/57 (1.8%)		4/20 (20%)		0/6 (0%)		0/15 (0%)
Dysaesthesia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Dysgeusia	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Headache	7/53 (13.2%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Hypoaesthesia	0/53 (0%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Lethargy	3/53 (5.7%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Loss of consciousness	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Migraine	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Muscle contractions involuntary	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Neuralgia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Peripheral sensory neuropathy	1/53 (1.9%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Sciatica	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Syncope	0/53 (0%)		2/57 (3.5%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Tremor	0/53 (0%)		0/57 (0%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Psychiatric disorders
Agitation	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Anxiety	3/53 (5.7%)		3/57 (5.3%)		2/20 (10%)		0/6 (0%)		1/15 (6.7%)
Confusional state	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Depression	3/53 (5.7%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		1/15 (6.7%)
Insomnia	1/53 (1.9%)		3/57 (5.3%)		0/20 (0%)		0/6 (0%)		3/15 (20%)
Libido decreased	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Renal and urinary disorders
Dysuria	0/53 (0%)		2/57 (3.5%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Glycosuria	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Haematuria	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Micturition urgency	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Pollakiuria	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)
Proteinuria	2/53 (3.8%)		1/57 (1.8%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/53 (1.9%)		2/57 (3.5%)		1/20 (5%)		1/6 (16.7%)		1/15 (6.7%)
Dysphonia	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Dyspnoea	5/53 (9.4%)		3/57 (5.3%)		2/20 (10%)		0/6 (0%)		2/15 (13.3%)
Hypoxia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Nasal dryness	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Painful respiration	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Pleural effusion	0/53 (0%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		0/15 (0%)
Reflux laryngitis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Rhinitis allergic	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Rhinorrhoea	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Sinus congestion	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Throat tightness	1/53 (1.9%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Skin and subcutaneous tissue disorders
Alopecia	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Dry skin	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Eczema	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Exfoliative rash	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Hyperhidrosis	0/53 (0%)		3/57 (5.3%)		1/20 (5%)		1/6 (16.7%)		1/15 (6.7%)
Night sweats	3/53 (5.7%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Palmar-plantar erythrodysaesthesia syndrome	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Rash	4/53 (7.5%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		2/15 (13.3%)
Skin exfoliation	1/53 (1.9%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Skin hyperpigmentation	0/53 (0%)		0/57 (0%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Skin lesion	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Skin ulcer	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Social circumstances
Alcohol use	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Vascular disorders
Axillary vein thrombosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Flushing	5/53 (9.4%)		4/57 (7%)		0/20 (0%)		0/6 (0%)		2/15 (13.3%)
Hypertension	3/53 (5.7%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		0/15 (0%)
Hypotension	1/53 (1.9%)		1/57 (1.8%)		2/20 (10%)		0/6 (0%)		1/15 (6.7%)
Lymphoedema	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Orthostatic hypotension	0/53 (0%)		1/57 (1.8%)		0/20 (0%)		0/6 (0%)		1/15 (6.7%)
Subclavian vein thrombosis	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)
Thrombophlebitis superficial	0/53 (0%)		0/57 (0%)		1/20 (5%)		0/6 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.