Efficacy and Safety of Pasireotide LAR (Long-acting Relea... | NCT01673646

Label	Type	Description	Intervention Names
Pasireotide LAR 20mg	Experimental	Enrolled patients were randomized to 20mg pasireotide LAR.	Drug: Pasireotide LAR
Pasireotide LAR 40mg	Experimental	Enrolled patients were randomized to 40mg pasireotide LAR.	Drug: Pasireotide LAR
Pasireotide LAR 60mg	Experimental	Enrolled patients were randomized to 60mg pasireotide LAR.	Drug: Pasireotide LAR

Name	Type	Description	Arm Group Labels	Other Names
Pasireotide LAR	Drug	Intramuscular administration of pasireotide LAR was repeated every month (1 month = 28 days) for 12 months in core phase. It was permitted to increase the dose up to 60 mg in a patient showing the following biochemical test results after 3 and 6 months of study treatment: mean GH levels ≥2.5 µg/L and/or IGF-1 > ULN. In the event of any problem with tolerability, it was permitted to reduce the next lower dosage level at any time.

Measure	Description	Time Frame
Total-group Response Rate at Month 3	Percentage of participants with a reduction of mean growth hormone (GH) levels to < 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses	Month 3

Measure	Description	Time Frame
Response Rate at Month 3 by Randomized Dose Level	Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3 months in each starting dose.	Month 3
GH Response at Month 3 by Randomized Dose

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Nagoya	Aichi-ken	466 8560	Japan
Novartis Investigative Site

ID	Title	Description
FG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
FG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jan 25, 2017	Apr 9, 2018

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

Total-group Response Rate at Month 3

Percentage of participants with a reduction of mean growth hormone (GH) levels to < 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses

The Full analysis Set (FAS): Comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 3

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG00033

Title

Denominators

Categories

Title	Measurements
	OG00018.2(7.0 to 35.5)

Secondary

Response Rate at Month 3 by Randomized Dose Level

Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3 months in each starting dose.

FAS: Comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 3

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts

Secondary

GH Response at Month 3 by Randomized Dose

Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L at 3 months.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 3

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts
Participants

Secondary

IGF-1 Response at Month 3 by Randomized Dose

Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 3 months.

Posted

Number

95% Confidence Interval

Percentage of participants

Month 3

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts
Participants

Secondary

Total-group Response Rate (GH & IGF-1) Over Time (Core Phase)

Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at 3, 6, 9 and 12 months

Posted

Number

95% Confidence Interval

Percentage of participants

Months 3, 6, 9 & 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Percentage of Overall Participants With the Reduction of GH Levels to <2.5 ug/L by Visit (Core Phase)

This refers to the percentage of participants with a reduction of growth hormone (GH) response rates to <2.5 ug/L over time.

Posted

Number

95% Confidence Interval

Percenage of participants

Months 3, 6, 9, 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Core Phase)

This refers to the percentage of participants with the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits by visit.

Posted

Number

95% Confidence Interval

Percentage of participants

Months 3, 6, 9, 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Summary of Pasireotide LAR PK Parameters of Ctrough & Cmax by Randomized Dose Level

Ctrough: The trough level concentration on day 28, 3 months post 1st, 2nd and 3rd injections of Pasireotide LAR.

Cmax: The maximum concentration 3 months post the 1st injection and 3rd injection of LAR.

The pharmacokinetic (PK) analysis set (PAS) consists of full analysis set (FAS) who have evaluable PK concentration data.

Posted

Mean

Standard Deviation

ng/mL

Ctrough: Day 28 after each injection 1-3, Cmax: 3 months after injections 1 and 3

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts
Participants

Secondary

Summary of Pasireotide LAR PK Parameter of Accumulation Ratio Randomized Dose Level

The accumulation ratio was calculated as a ratio of (Ctrough day28, 3rd injection/Ctrough day28, 1st injection).

PAS: Consists of full analysis set (FAS) who have evaluable PK concentration data

Posted

Mean

Standard Deviation

ratio

Day 28 after injections 1 and 3

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts
Participants

Secondary

Change of Tumor Volume From Baseline

This shows the change in tumor volume from baseline to month 6 and from baseline to month 12 in patients treated with pasireotide LAR.

FAS: Comprises all patients to whom study treatment has been assigned by randomization. Protocol allowed to change treatment dose (eg, 20mg -> 40mg ->20mg -> 40mg ->60mg) based on efficacy and safety after 3month treatment. So we combined Arms/groups.

Posted

Median

Full Range

mm^3

Baseline, Months 6 , 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Change in Mean GH Levels From Baseline

This shows the change in mean GH levels from baseline in median GH levels by visit.

Posted

Median

Full Range

ug/L

Baseline, Months 2.75, 3, 6, 9, 12, 18, 24

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Change in Ring Size From Baseline

Change of clinical signs from baseline: ring size. In Japan, ring sizes are specified using a numerical scale, that only has whole sizes, and does not have simple linear correlation with diameter or circumference. Only numbers are used ranging from 1 to 27. For instance, a ring size of 1 in Japan is equivalent to an inside circumference ring size of 38.86 mm and a ring size of 27 in Japan is equivalent to an inside circumference ring size of 70.15 mm.

Posted

Median

Full Range

other - Japanese ring size number

Baseline, Months 3, 6, 9, 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Acromegaly Symptoms or Pituitary Gigantism (Core Phase)

Number of participants with a change of clinical signs from baseline (BL): headache (HA), fatigue (FA), perspiration (PE), paresthesias (PA), osteoarthralgia (OS)

Full analysis set (FAS) comprises all patients to whom study treatment has been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the study treatment they have been assigned to during the randomization procedure.

Posted

Count of Participants

Participants

12 Months (Core phase)

ID	Title	Description
OG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
OG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
OG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.

Units	Counts

Secondary

Change From Baseline in Prolactin

Change in prolactin levels from baseline

Posted

Median

Full Range

pmol/L

Baseline, Months 3, 6, 9, 12

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Total-group Response Rate by Visit (Extension Phase)

Percentage of participants with a reduction of mean GH levels to < 2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) a18 and 24 months of study treatment.

FAS: Comprises all patients to whom study treatment has been assigned by randomization. The protocol allowed frequent dose changes even extension phase. In this case, separate data is not meaningful.

Posted

Number

95% Confidence Interval

Percentage of participants

Months 18, 24

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Percentage of Overall Participants With the Reduction of Mean GH Levels to <2.5 ug/L by Visit (Extension Phase)

Percentage of participants with a reduction of mean GH levels to < 2.5µg/L at 18 and 24 months of study treatment

FAS: Comprises all patients to whom study treatment has been assigned by randomization. The protocol allowed frequent dose changes even extension phase. In this case, separate data is not meaningful.

Posted

Number

95% Confidence Interval

Percentage of participants

Months 18, 24

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Percentage of Overall Participants With the Normalization of IGF-1 by Visit (Extension Phase)

Percentage of participants with the normalization of IGF-1 to within normal limits (age and sex related) at 18 and 24 months of study. treatment

FAS: Comprises all patients to whom study treatment has been assigned by randomization. The protocol allowed frequent dose changes even extension phase. In this case, separate data is not meaningful.

Posted

Number

95% Confidence Interval

Percentage of participants

Months 18, 24

ID	Title	Description
OG000	Pasireotide LAR - All Participants	All patients randomized regardless of pasireotide LAR dose.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Mean GH by Visit and SSA Uncontrolled Status (Extension Phase)

This shows a change of mean GH levels and somatostatin analogues (SSAs) from baseline in extension phase

Posted

Median

Full Range

ug/L

Baselnine, Months 2.75, 3, 6, 9, 12, 18, 24

ID	Title	Description
OG000	SSA Uncontrolled	Somatostatin analogue (SSA) uncontrolled population composes of patients who were pre-treated with SSA for >= 12 weeks.
OG001	Others	Patients who were pre-treated with SSA for < 12 weeks or were not pre-treated with SSA are considered as others.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG0032 affected33 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Eustachian tube patulous	Ear and labyrinth disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Thyroiditis	Endocrine disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Arteriosclerotic retinopathy	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Blepharitis	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Conjunctival hyperaemia	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Diabetic retinopathy	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Eye discharge	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Pterygium	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Retinal detachment	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Abdominal symptom	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Anal fistula	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0013 affected11 at risk EG0022 affected11 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0012 affected11 at risk EG0022 affected11 at risk EG003
Faeces pale	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Gastrointestinal motility disorder	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0023 affected11 at risk EG003
Pancreatic duct dilatation	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Periodontal disease	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Proctitis	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0021 affected11 at risk EG003
Fatigue	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Malaise	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Oedema peripheral	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Pyrexia	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Biliary dilatation	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0012 affected11 at risk EG0023 affected11 at risk EG003
Gallbladder enlargement	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Gallbladder polyp	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Hepatic cyst	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Liver disorder	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Influenza	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0007 affected11 at risk EG0016 affected11 at risk EG0028 affected11 at risk EG003
Paronychia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Periodontitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Skin infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Excoriation	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Ulna fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Venomous sting	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Blood corticotrophin decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Blood glucose decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Blood glucose increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Blood uric acid increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Blood urine present	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0023 affected11 at risk EG003
Insulin-like growth factor decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Lipase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Liver function test abnormal	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Weight decreased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Weight increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected11 at risk EG0012 affected11 at risk EG0022 affected11 at risk EG003
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0022 affected11 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected11 at risk EG0014 affected11 at risk EG0024 affected11 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0012 affected11 at risk EG0022 affected11 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Neoplasm skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Pituitary tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Altered state of consciousness	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Diabetic neuropathy	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Migraine	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Tension headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Ureterolithiasis	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Cervical polyp	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Menopausal symptoms	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Premenstrual syndrome	Reproductive system and breast disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0012 affected11 at risk EG0020 affected11 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0022 affected11 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0013 affected11 at risk EG0020 affected11 at risk EG003
Miliaria	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0021 affected11 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Toxic skin eruption	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Hypertension	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Hypotension	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003

ID	Term
D000172	Acromegaly
D005877	Gigantism
D006130	Growth Disorders
D010911	Pituitary Neoplasms

ID	Term
D001849	Bone Diseases, Endocrine
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D006964	Hyperpituitarism
D010900	Pituitary Diseases
D007027	Hypothalamic Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D004700	Endocrine System Diseases
D001848	Bone Diseases, Developmental
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D007029	Hypothalamic Neoplasms
D015173	Supratentorial Neoplasms
D001932	Brain Neoplasms
D016543	Central Nervous System Neoplasms
D009423	Nervous System Neoplasms

ID	Title	Description
BG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.
BG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.
BG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pasireotide LAR 20mg	Enrolled patients were randomized to 20mg pasireotide LAR.	11	3	11	11	11
EG001	Pasireotide LAR 40mg	Enrolled patients were randomized to 40mg pasireotide LAR.	11	3	11	11	11
EG002	Pasireotide LAR 60mg	Enrolled patients were randomized to 60mg pasireotide LAR.	11	5	11	11	11
EG003	Pasireotide LAR - All Participants (All Patieents)	Patients who were randomized to the study - regardless of whether they were in the Core or Extension phase.	33	11	33	33	33

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Sudden hearing loss	Ear and labyrinth disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG0031 affected33 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Influenza	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Meningitis bacterial	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0021 affected11 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003
Persistent depressive disorder	Psychiatric disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected11 at risk EG0010 affected11 at risk EG0020 affected11 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected11 at risk EG0011 affected11 at risk EG0020 affected11 at risk EG003