Efficacy and Safety of Pasireotide Long Acting Release vs... | NCT00690430

ID	Type	Description	Link
2007-000739-25	EudraCT Number

Label	Type	Description	Intervention Names
Pasireotide LAR	Active Comparator	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
Octreotide LAR	Active Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Pasireotide	Drug	Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed	Pasireotide LAR

Measure	Description	Time Frame
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.	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.	Month 6

Measure	Description	Time Frame
Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.	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.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Scottsdale Healthcare/TGen Clinical Research Service TGen Clinical Research Service		Scottsdale	Arizona	85258	United States

Label	URL
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.	View source

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00043 OG00145

Title

Denominators

Categories

Diarrhea and Flushing (N=37, 39)

Title	Measurements
	OG00013.5(4.5 to 28.8) OG00128.2(15.0 to 44.9)

Diarrhea (N=2, 5)

Title	Measurements
	OG000

Secondary

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

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.

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.

Posted

Mean

Standard Deviation

Percentage of Episodes

6 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.

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.

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.

Posted

Mean

Standard Deviation

Percentage of Episodes

6 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.

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.

Posted

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Objective Tumor Response Rate Assessed by Investigator

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.

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Month 6

ID	Title	Description
OG000	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.

Secondary

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

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 6

ID	Title	Description
OG000	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.

Secondary

Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire

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.

Posted

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Units

Secondary

Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression

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.

Posted

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response

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.

Posted

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements

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.

Posted

Month 6

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Carcinoid heart disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG0030 affected6 at risk EG0040 affected15 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Cardiomyopathy	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Endocardial fibrosis	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Anorectal disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Intestinal infarction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Pneumoperitoneum	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Condition aggravated	General disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Device dislocation	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Device infusion issue	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Localised oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Malaise	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Medical device complication	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Cholestasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Hepatomegaly	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Clostridial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Infectious peritonitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Blood pH increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Liver function test abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Troponin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0012 affected57 at risk EG0021 affected20 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0012 affected57 at risk EG0021 affected20 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Carcinoid tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Carcinoid tumour of the gastrointestinal tract	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Metastases to chest wall	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Metastatic carcinoid tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Central nervous system lesion	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Nephritis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Renal failure chronic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Urinary tract disorder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Respite care	Social circumstances	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Flushing	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Vein disorder	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG0030 affected6 at risk EG0040 affected15 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Aortic valve sclerosis	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Bundle branch block right	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dilatation ventricular	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Mitral valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0015 affected57 at risk EG0020 affected20 at risk EG003
Pulmonary valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Birth mark	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0022 affected20 at risk EG003
Conjunctivitis	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dry eye	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Eye pain	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Glaucoma	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Visual impairment	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected53 at risk EG0018 affected57 at risk EG0021 affected20 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0014 affected57 at risk EG0021 affected20 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00012 affected53 at risk EG0019 affected57 at risk EG0024 affected20 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0022 affected20 at risk EG003
Faecal incontinence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0023 affected20 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0012 affected57 at risk EG0024 affected20 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected53 at risk EG0017 affected57 at risk EG0024 affected20 at risk EG003
Painful defaecation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Proctitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Rectal ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Short-bowel syndrome	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0017 affected57 at risk EG0024 affected20 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0005 affected53 at risk EG0016 affected57 at risk EG0024 affected20 at risk EG003
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Chills	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00011 affected53 at risk EG0018 affected57 at risk EG0026 affected20 at risk EG003
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Injection site pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Localised oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Malaise	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0014 affected57 at risk EG0020 affected20 at risk EG003
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0009 affected53 at risk EG0015 affected57 at risk EG0025 affected20 at risk EG003
Pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0024 affected20 at risk EG003
Biliary dilatation	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0004 affected53 at risk EG0014 affected57 at risk EG0021 affected20 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Biliary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Cystitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Ear infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Gastrointestinal bacterial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Incision site infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0015 affected57 at risk EG0020 affected20 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Tooth infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0022 affected20 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Tooth fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Albumin urine present	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0015 affected57 at risk EG0022 affected20 at risk EG003
Blood bilirubin increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Blood calcium increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Blood glucose increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Blood magnesium decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Blood testosterone decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Blood triglycerides increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Blood urea increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Blood urine present	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Glycosylated haemoglobin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Haematocrit increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Haemoglobin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Red blood cell count increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0008 affected53 at risk EG0014 affected57 at risk EG0022 affected20 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0014 affected57 at risk EG0021 affected20 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0012 affected57 at risk EG0022 affected20 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0006 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00015 affected53 at risk EG0013 affected57 at risk EG0027 affected20 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0023 affected20 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0023 affected20 at risk EG003
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0007 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0014 affected57 at risk EG0020 affected20 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Aphasia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Aphonia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Cervicobrachial syndrome	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected53 at risk EG0011 affected57 at risk EG0024 affected20 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0007 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Lethargy	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Muscle contractions involuntary	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Neuralgia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Sciatica	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0021 affected20 at risk EG003
Tremor	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0022 affected20 at risk EG003
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0013 affected57 at risk EG0020 affected20 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0012 affected57 at risk EG0020 affected20 at risk EG003
Glycosuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected53 at risk EG0011 affected57 at risk EG0021 affected20 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0012 affected57 at risk EG0021 affected20 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0005 affected53 at risk EG0013 affected57 at risk EG0022 affected20 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Painful respiration	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Reflux laryngitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Throat tightness	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0013 affected57 at risk EG0021 affected20 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0004 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0020 affected20 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Alcohol use	Social circumstances	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Axillary vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Flushing	Vascular disorders	MedDRA	Systematic Assessment	EG0005 affected53 at risk EG0014 affected57 at risk EG0020 affected20 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0003 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected53 at risk EG0011 affected57 at risk EG0022 affected20 at risk EG003
Lymphoedema	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0011 affected57 at risk EG0020 affected20 at risk EG003
Subclavian vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected53 at risk EG0010 affected57 at risk EG0021 affected20 at risk EG003

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue

ID	Term
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	15	53	50	53
EG001	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.	19	57	48	57
EG002	Extension Phase 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.	9	20	19	20
EG003	Extension Phase 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.	2	6	5	6
EG004	Crossover to 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.	7	15	12	15