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PAOLA: Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01137682
Collaborator
(none)
198
Enrollment
60
Locations
3
Arms
79.4
Actual Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of pasireotide LAR 40 and 60 mg versus octreotide LAR or lanreotide ATG in patients with inadequately controlled acromegaly.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
198 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized, Parallel-group Study to Assess the Efficacy and Safety of Double-blind Pasireotide LAR 40 mg and Pasireotide LAR 60 mg Versus Open-label Octreotide LAR or Lanreotide ATG in Patients With Inadequately Controlled Acromegaly
Actual Study Start Date :
Jul 19, 2010
Actual Primary Completion Date :
Jan 22, 2013
Actual Study Completion Date :
Feb 28, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pasireotide LAR 40 mg

Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

Drug: Pasireotide
Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
Other Names:
  • SOM230

    		•
    Experimental: Pasireotide LAR 60 mg

    Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)

    Drug: Pasireotide
    Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks
    Other Names:
  • SOM230

    		•
    Active Comparator: Control arm (octreotide or lanreotide)

    If a patient is randomized to the open label arm the investigator will either: be instructed to contact a Novartis delegate to initiate shipment of either octreotide LAR 30 mg or lanreotide ATG 120 mg from a Novartis or designee depot to the site, or continue to dispense either octreotide LAR 30 mg or lanreotide ATG 120 mg available at the institution to the patient if permitted by local regulations.

    Drug: octreotide LAR 30mg
    In an open-label, active control arm, continue on the same treatment with octreotide LAR 30 mg every 28 ± 2 days as received for at least 6 months prior to randomization

    Drug: lanreotide ATG 120mg
    In an open-label, active control arm, continue on the same treatment with lanreotide ATG 120 mg every 28 ± 2 days as received for at least 6 months prior to randomization

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1. [At 24 weeks]

      The primary objective of this study was to compare the percentage of patients achieving biochemical control (defined as mean GH levels <2.5 µg/L and normalization of sex- and age- adjusted IGF-1) at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continued treatment with octreotide LAR 30 mg or lanreotide autogel (ATG) 120 mg. The primary efficacy variable is the proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks.

    Secondary Outcome Measures

    1. Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) [Extension baseline up to approximately week 268]

      The percentage of patients achieving mean growth hormone (GH) levels < 2.5 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (extension full analysis set)

    2. Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set). [Extension baseline up to approximately week 268]

      The percentage of patients achieving normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

    3. Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) [Extension baseline up to approximately week 268]

      The percentage of patients achieving mean growth hormone (GH) levels < 2.5 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

    4. Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) [Extension baseline up to approximately week 268]

      The percentage of patients achieving mean growth hormone (GH) levels < 1.0 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set

    5. Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) [Extension baseline up to approximately week 268]

      The percentage of patients achieving mean growth hormone (GH) levels < 1.0 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)

    6. Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) [CORE baseline up to approximately 24 weeks]

    7. Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) [CORE and extension baseline up to approximately 268 weeks]

      Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm.

    8. Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set) [CORE baseline up to approximately 24 weeks]

      Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range

    9. Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) [CORE and extension baseline up to approximately 268 weeks]

      Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm. Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range

    10. Duration of the First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set) [CORE baseline up to approximately 268 weeks]

      n is the number of patients achieving response criteria. The weeks correspond to duration of first response (in weeks) for patients achieving biomedical control. Median and 95% CI are derived from Kaplan-Meier curves. Kaplan-Meier estimates [95% CI] at each time point are estimates of probability of response.

    11. Time to First Response (Weeks) by Treatment for Patients Achieving a Reduction of Mean GH Level to < 2.5 µg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly [CORE baseline up to approximately 268 weeks]

      Time to first response is defined as the time from the date of first dose to the date of first occurrence of a reduction of mean GH < 2.5 µg/L and the normalization of IGF-1. The weeks correspond to time taken to achieve first mean GH < 2.5 µg/L and the normalization of IGF-1.

    12. Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set) [CORE baseline up to approximately 24 weeks]

      Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid.

    13. Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set) [CORE Baseline and extension baseline up to approximately 268 weeks]

      Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid.

    14. Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set) [Extension baseline up to approximately 196 weeks]

      PK samples were collected for those patients treated with pasireotide LAR in the core study and who continued on pasireotide LAR in the extension phase. PK samples were collected before the injection of pasireotide LAR only at weeks 112 and 196. PK samples were also collected at weeks 48 and 132 only for all patients treated with octreotide LAR 30 mg or lanreotide ATG 120 mg in the core study who started treatment with pasireotide LAR in the extension study. Blood samples (2.5 mL each sample) were collected to yield 1-mL plasma for analysis of pasireotide LAR oncentration.

    Eligibility Criteria

    Criteria

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

    1. Patients with written informed consent prior to any study related activity

    2. Patients who had inadequately controlled acromegaly as defined by a mean GH concentration of a 5-point profile over a 2-hour period > 2.5 µg/L and sex- and age-adjusted IGF-1 > 1.3 x upper limit of normal (ULN)

    3. Patients who had been treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to visit 1 (screening). The maximum indicated dose for octreotide LAR was 30mg and for lanreotide ATG iwas120 mg

    4. Patients who had a diagnosis of pituitary micro- or macro adenoma. Patients could have been previously submitted to surgery

    5. Patients who completed the 24-week treatment period in core according to the requirements of the core study protocol or corresponding amendments could enter extension

    Exclusion Criteria:

    1. Patients who had received pasireotide (SOM 230) prior to enrolment

    2. Concomitant treatment with Growth Hormone Receptor (GHR)-antagonist or dopamine agonists unless concomitant treatment was discontinued 8 weeks prior to visit 1 (screening)(8 weeks wash out period). Such patients must have been treated with octreotide LAR 30 mg or lanreotide ATG 120 mg monotherapy continuously for a minimum of 6 months prior to starting combination therapy and they should have been inadequately controlled on monotherapy.

    3. Patients who had compression of the optic chiasm causing acute clinically significant visual field defects

    4. Patients who required a surgical intervention for relief of any sign or symptom associated with tumor compression

    5. Patients who had received pituitary irradiation within 10 years prior to visit 1 (screening).

    6. Patients who had undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening).

    7. Patients who were hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Michigan Ann Arbor Michigan United States 48109
    2 Oregon Health & Science University Portland Oregon United States 97239
    3 University of Texas Southwestern Medical Center Division of Hematology/Oncolog Dallas Texas United States 75235
    4 Swedish Neuroscience Institute 550 17th Avenue, Suite 500 Seattle Washington United States 98122
    5 Novartis Investigative Site Caba Buenos Aires Argentina C1405BCH
    6 Novartis Investigative Site Edegem Antwerpen Belgium 2650
    7 Novartis Investigative Site Brussels Belgium BE-B-1200
    8 Novartis Investigative Site Gent Belgium 9000
    9 Novartis Investigative Site Leuven Belgium 3000
    10 Novartis Investigative Site Fortaleza CE Brazil 60430 370
    11 Novartis Investigative Site Sao Luis MA Brazil 65020-070
    12 Novartis Investigative Site Rio de Janeiro RJ Brazil 21941-913
    13 Novartis Investigative Site Joinville SC Brazil 89201260
    14 Novartis Investigative Site Botucatu SP Brazil 18618-970
    15 Novartis Investigative Site Campinas SP Brazil 13083-970
    16 Novartis Investigative Site Sao Paulo SP Brazil 05403 000
    17 Novartis Investigative Site São Paulo SP Brazil 04038-002
    18 Novartis Investigative Site Sherbrooke Quebec Canada J1H 5N4
    19 Novartis Investigative Site Bogota Cundinamarca Colombia 111411
    20 Novartis Investigative Site Bogotá Colombia 00000
    21 Novartis Investigative Site Cali Colombia
    22 Novartis Investigative Site Toulouse Cedex 9 France 31000
    23 Novartis Investigative Site Bron Cedex France 69677
    24 Novartis Investigative Site Dijon France 21034
    25 Novartis Investigative Site Le Kremlin Bicetre France 94275
    26 Novartis Investigative Site Lille France 59037
    27 Novartis Investigative Site Marseille France 13005
    28 Novartis Investigative Site Paris France 75571
    29 Novartis Investigative Site Pessac Cedex France 33604
    30 Novartis Investigative Site Rennes Cedex France 35022
    31 Novartis Investigative Site Saint Herblain - Nantes France 44093
    32 Novartis Investigative Site Erlangen Germany 91054
    33 Novartis Investigative Site Hamburg Germany 22587
    34 Novartis Investigative Site Muenchen Germany 80336
    35 Novartis Investigative Site Wurzburg Germany 97080
    36 Novartis Investigative Site Petach Tikva Israel 49100
    37 Novartis Investigative Site Genova GE Italy 16132
    38 Novartis Investigative Site Messina ME Italy 98125
    39 Novartis Investigative Site Roma RM Italy 00168
    40 Novartis Investigative Site Torino TO Italy 10126
    41 Novartis Investigative Site Napoli Italy 80131
    42 Novartis Investigative Site Bergen Norway NO-5021
    43 Novartis Investigative Site Oslo Norway NO-0379
    44 Novartis Investigative Site Gdansk Poland 80-952
    45 Novartis Investigative Site Poznan Poland 60-355
    46 Novartis Investigative Site Wroclaw Poland 50 367
    47 Novartis Investigative Site Bucuresti Romania 011863
    48 Novartis Investigative Site Barnaul Russian Federation 656024
    49 Novartis Investigative Site Moscow Russian Federation 101990
    50 Novartis Investigative Site Moscow Russian Federation 117036
    51 Novartis Investigative Site Tyumen Russian Federation 625023
    52 Novartis Investigative Site Jeddah Saudi Arabia 21423
    53 Novartis Investigative Site Riyadh Saudi Arabia 11211
    54 Novartis Investigative Site Sevilla Andalucia Spain 41013
    55 Novartis Investigative Site Barcelona Catalunya Spain 08035
    56 Novartis Investigative Site Alicante Comunidad Valenciana Spain 03010
    57 Novartis Investigative Site Altunizade Turkey 34662
    58 Novartis Investigative Site Antalya Turkey 07070
    59 Novartis Investigative Site Izmir Turkey 35340
    60 Novartis Investigative Site Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01137682
    Other Study ID Numbers:
    • CSOM230C2402
    • EUDRACT 2009-016722-13
    First Posted:
    Jun 4, 2010
    Last Update Posted:
    Apr 5, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Acromegaly
    hormone disorder
    growth hormone
    insulin like growth factor-1
    pituitary tumor
    pasireotide
    SOM230
    Additional relevant MeSH terms:
    Acromegaly
    Octreotide
    Lanreotide
    Pasireotide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail One hundred ninety-eight patients were randomized and 5 patients in CORE and 1 patient in extension did not receive any study treatment
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg Control Arm (Octreotide or Lanreotide)
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
    Period Title: Overall Study
    STARTED 65 65 68
    Not Treated 2 2 1
    Treated 63 63 67
    Completed 24-Week Core Phase 59 57 65
    Not Continuing Into Extension 2 3 2
    Continuing Into Extension 57 54 63
    Safety Set - CORE 63 62 66
    Safety Set - Extension 57 54 62
    COMPLETED 28 25 34
    NOT COMPLETED 37 40 34

    Baseline Characteristics

    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg Control Arm (Octreotide or Lanreotide) Total
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days Total of all reporting groups
    Overall Participants 65 65 68 198
    Age, Customized (Number) [Number]
    <65 Years
    62
    95.4%
    57
    87.7%
    63
    92.6%
    182
    91.9%
    ≥ 65 Years
    3
    4.6%
    8
    12.3%
    5
    7.4%
    16
    8.1%
    Sex: Female, Male (Count of Participants)
    Female
    38
    58.5%
    35
    53.8%
    38
    55.9%
    111
    56.1%
    Male
    27
    41.5%
    30
    46.2%
    30
    44.1%
    87
    43.9%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    53
    81.5%
    52
    80%
    56
    82.4%
    161
    81.3%
    Black
    3
    4.6%
    8
    12.3%
    4
    5.9%
    15
    7.6%
    Other
    4
    6.2%
    3
    4.6%
    7
    10.3%
    14
    7.1%
    Native American
    2
    3.1%
    1
    1.5%
    1
    1.5%
    4
    2%
    Asian
    3
    4.6%
    1
    1.5%
    0
    0%
    4
    2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.
    Description The primary objective of this study was to compare the percentage of patients achieving biochemical control (defined as mean GH levels <2.5 µg/L and normalization of sex- and age- adjusted IGF-1) at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continued treatment with octreotide LAR 30 mg or lanreotide autogel (ATG) 120 mg. The primary efficacy variable is the proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks.
    Time Frame At 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg Control Arm (Octreotide or Lanreotide)
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
    Measure Participants 65 65 68
    Number (95% Confidence Interval) [percentage of participants]
    15.4
    23.7%
    20.0
    30.8%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pasireotide LAR 40 mg, Control Arm (Octreotide or Lanreotide)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method Regression, Logistic
    Comments An exact logistic regression model that adjusts for the randomization stratification factors was used to test the null hypothesis.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.63
    Confidence Interval (2-Sided) 95%
    3.32 to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pasireotide LAR 60 mg, Control Arm (Octreotide or Lanreotide)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments An exact logistic regression model that adjusts for the randomization stratification factors was used to test the null hypothesis.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 23.03
    Confidence Interval (2-Sided) 95%
    4.72 to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
    Description The percentage of patients achieving mean growth hormone (GH) levels < 2.5 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (extension full analysis set)
    Time Frame Extension baseline up to approximately week 268

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16
    19.3
    29.7%
    25.9
    39.8%
    19.4
    28.5%
    Week 28
    17.5
    26.9%
    25.9
    39.8%
    19.4
    28.5%
    Week 40
    21.1
    32.5%
    27.8
    42.8%
    17.7
    26%
    Week 52
    21.1
    32.5%
    29.6
    45.5%
    21.0
    30.9%
    Week 64
    22.8
    35.1%
    20.4
    31.4%
    25.8
    37.9%
    Week 76
    21.1
    32.5%
    29.6
    45.5%
    27.4
    40.3%
    Week 88
    24.6
    37.8%
    31.5
    48.5%
    25.8
    37.9%
    Week 100
    24.6
    37.8%
    24.1
    37.1%
    32.3
    47.5%
    Week 112
    24.6
    37.8%
    25.9
    39.8%
    25.8
    37.9%
    Week 124
    21.1
    32.5%
    24.1
    37.1%
    25.8
    37.9%
    Week 136
    15.8
    24.3%
    24.1
    37.1%
    29.0
    42.6%
    Week 148
    21.1
    32.5%
    20.4
    31.4%
    29.0
    42.6%
    Week 160
    19.3
    29.7%
    20.4
    31.4%
    30.6
    45%
    Week 172
    22.8
    35.1%
    20.4
    31.4%
    21.0
    30.9%
    Week 184
    17.5
    26.9%
    20.4
    31.4%
    17.7
    26%
    Week 196
    15.8
    24.3%
    20.4
    31.4%
    24.2
    35.6%
    Week 208
    17.5
    26.9%
    18.5
    28.5%
    19.4
    28.5%
    Week 220
    21.1
    32.5%
    11.1
    17.1%
    14.5
    21.3%
    Week 232
    14.0
    21.5%
    14.8
    22.8%
    14.5
    21.3%
    Week 244
    14.0
    21.5%
    7.4
    11.4%
    11.3
    16.6%
    Week 256
    10.5
    16.2%
    7.4
    11.4%
    3.2
    4.7%
    Week 268
    5.3
    8.2%
    5.6
    8.6%
    1.6
    2.4%
    3. Secondary Outcome
    Title Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set).
    Description The percentage of patients achieving normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)
    Time Frame Extension baseline up to approximately week 268

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16
    33.3
    51.2%
    29.0
    44.6%
    25.8
    37.9%
    Week 28
    29.8
    45.8%
    33.3
    51.2%
    22.6
    33.2%
    Week 40
    36.8
    56.6%
    37.0
    56.9%
    24.2
    35.6%
    Week 52
    28.1
    43.2%
    33.3
    51.2%
    25.8
    37.9%
    Week 64
    33.3
    51.2%
    27.8
    42.8%
    29.0
    42.6%
    Week 76
    26.3
    40.5%
    35.2
    54.2%
    29.0
    42.6%
    Week 88
    28.1
    43.2%
    35.2
    54.2%
    25.8
    37.9%
    Week 100
    31.6
    48.6%
    29.6
    45.5%
    32.3
    47.5%
    Week 112
    31.6
    48.6%
    27.8
    42.8%
    30.6
    45%
    Week 124
    24.6
    37.8%
    31.5
    48.5%
    29.0
    42.6%
    Week 136
    21.1
    32.5%
    25.9
    39.8%
    37.1
    54.6%
    Week 148
    26.3
    40.5%
    22.2
    34.2%
    33.9
    49.9%
    Week 160
    24.6
    37.8%
    25.9
    39.8%
    33.9
    49.9%
    Week 172
    26.3
    40.5%
    22.2
    34.2%
    22.6
    33.2%
    Week 184
    19.3
    29.7%
    22.2
    34.2%
    22.6
    33.2%
    Week 196
    24.6
    37.8%
    22.2
    34.2%
    27.4
    40.3%
    Week 208
    22.8
    35.1%
    22.2
    34.2%
    21.0
    30.9%
    Week 220
    22.8
    35.1%
    11.1
    17.1%
    19.4
    28.5%
    Week 232
    14.0
    21.5%
    14.8
    22.8%
    17.7
    26%
    Week 244
    14.0
    21.5%
    9.3
    14.3%
    14.5
    21.3%
    Week 256
    12.3
    18.9%
    7.4
    11.4%
    6.5
    9.6%
    Week 268
    5.3
    8.2%
    5.6
    8.6%
    1.6
    2.4%
    4. Secondary Outcome
    Title Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
    Description The percentage of patients achieving mean growth hormone (GH) levels < 2.5 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)
    Time Frame Extension baseline up to approximately week 268

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): comprised all patients who were randomized. Following the intent-to-treat principle, patients were analyzed according to the study drug they were assigned to at randomization and actual stratum.
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Control Arm (Octreotide or Lanreotide) Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled
    Measure Participants 57 54 62
    Week 16
    38.6
    59.4%
    55.6
    85.5%
    33.9
    49.9%
    Week 28
    40.4
    62.2%
    44.4
    68.3%
    43.5
    64%
    Week 40
    38.6
    59.4%
    42.6
    65.5%
    40.3
    59.3%
    Week 52
    38.6
    59.4%
    46.3
    71.2%
    41.9
    61.6%
    Week 64
    40.4
    62.2%
    37.0
    56.9%
    41.9
    61.6%
    Week 76
    33.3
    51.2%
    44.4
    68.3%
    45.2
    66.5%
    Week 88
    40.4
    62.2%
    42.6
    65.5%
    45.2
    66.5%
    Week 100
    40.4
    62.2%
    40.7
    62.6%
    46.8
    68.8%
    Week 112
    36.8
    56.6%
    44.4
    68.3%
    40.3
    59.3%
    Week 124
    40.4
    62.2%
    31.5
    48.5%
    41.9
    61.6%
    Week 136
    36.8
    56.6%
    35.2
    54.2%
    43.5
    64%
    Week 148
    40.4
    62.2%
    33.3
    51.2%
    43.5
    64%
    Week 160
    38.6
    59.4%
    33.3
    51.2%
    40.3
    59.3%
    Week 172
    40.4
    62.2%
    37.0
    56.9%
    38.7
    56.9%
    Week 184
    33.3
    51.2%
    31.5
    48.5%
    33.9
    49.9%
    Week 196
    29.8
    45.8%
    29.6
    45.5%
    35.5
    52.2%
    Week 208
    31.6
    48.6%
    24.1
    37.1%
    25.8
    37.9%
    Week 220
    29.8
    45.8%
    18.5
    28.5%
    22.6
    33.2%
    Week 232
    24.6
    37.8%
    18.5
    28.5%
    21.0
    30.9%
    Week 244
    19.3
    29.7%
    11.1
    17.1%
    12.9
    19%
    Week 256
    15.8
    24.3%
    9.3
    14.3%
    6.5
    9.6%
    Week 268
    7.0
    10.8%
    5.6
    8.6%
    3.2
    4.7%
    5. Secondary Outcome
    Title Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
    Description The percentage of patients achieving mean growth hormone (GH) levels < 1.0 μg/L and normalization of sex and age-adjusted IGF-1 was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Total insulin-like growth factor (IGF-1) levels were assessed with one pre-dose sample at the same visits as GH. Concomitant medication known to affect GH or IGF-1 levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set
    Time Frame Extension baseline up to approximately week 268

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16
    10.5
    16.2%
    16.7
    25.7%
    6.5
    9.6%
    Week 28
    8.8
    13.5%
    14.8
    22.8%
    8.1
    11.9%
    Week 40
    10.5
    16.2%
    9.3
    14.3%
    4.8
    7.1%
    Week 52
    8.8
    13.5%
    13.0
    20%
    4.8
    7.1%
    Week 64
    8.8
    13.5%
    13.0
    20%
    9.7
    14.3%
    Week 76
    10.5
    16.2%
    13.0
    20%
    6.5
    9.6%
    Week 88
    7.0
    10.8%
    20.4
    31.4%
    4.8
    7.1%
    Week 100
    12.3
    18.9%
    14.8
    22.8%
    8.1
    11.9%
    Week 112
    14.0
    21.5%
    20.4
    31.4%
    9.7
    14.3%
    Week 124
    7.0
    10.8%
    14.8
    22.8%
    8.1
    11.9%
    Week 136
    3.5
    5.4%
    18.5
    28.5%
    11.3
    16.6%
    Week 148
    10.5
    16.2%
    14.8
    22.8%
    8.1
    11.9%
    Week 160
    8.8
    13.5%
    14.8
    22.8%
    9.7
    14.3%
    Week 172
    14.0
    21.5%
    13.0
    20%
    8.1
    11.9%
    Week 184
    7.0
    10.8%
    13.0
    20%
    3.2
    4.7%
    Week 196
    8.8
    13.5%
    13.0
    20%
    8.1
    11.9%
    Week 208
    8.8
    13.5%
    9.3
    14.3%
    6.5
    9.6%
    Week 220
    10.5
    16.2%
    7.4
    11.4%
    6.5
    9.6%
    Week 232
    10.5
    16.2%
    3.7
    5.7%
    4.8
    7.1%
    Week 244
    8.8
    13.5%
    3.7
    5.7%
    6.5
    9.6%
    Week 256
    8.8
    13.5%
    3.7
    5.7%
    3.2
    4.7%
    Week 268
    1.8
    2.8%
    3.7
    5.7%
    1.6
    2.4%
    6. Secondary Outcome
    Title Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
    Description The percentage of patients achieving mean growth hormone (GH) levels < 1.0 μg/L was calculated with two sided 95% confidence interval. All GH assessments were based on a 5-point mean growth hormone (GH) assessed from a 2-hour profile. Scheduled time points for blood sampling were pre-dose at 0, 30, 60, 90 and 120 minutes. Concomitant medication known to affect GH levels were allowed in patients who were not biochemically controlled after at least one year treatment with pasireotide LAR monotherapy: dopamine agonists and growth hormone receptor antagonists (Extension full analysis set)
    Time Frame Extension baseline up to approximately week 268

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16
    14.0
    21.5%
    27.8
    42.8%
    8.1
    11.9%
    Week 28
    14.0
    21.5%
    22.2
    34.2%
    9.7
    14.3%
    Week 40
    14.0
    21.5%
    13.0
    20%
    4.8
    7.1%
    Week 52
    12.3
    18.9%
    22.2
    34.2%
    9.7
    14.3%
    Week 64
    15.8
    24.3%
    18.5
    28.5%
    11.3
    16.6%
    Week 76
    12.3
    18.9%
    22.2
    34.2%
    11.3
    16.6%
    Week 88
    15.8
    24.3%
    22.2
    34.2%
    11.3
    16.6%
    Week 100
    17.5
    26.9%
    20.4
    31.4%
    17.7
    26%
    Week 112
    17.5
    26.9%
    25.9
    39.8%
    16.1
    23.7%
    Week 124
    12.3
    18.9%
    16.7
    25.7%
    14.5
    21.3%
    Week 136
    8.8
    13.5%
    25.9
    39.8%
    14.5
    21.3%
    Week 148
    14.0
    21.5%
    16.7
    25.7%
    14.5
    21.3%
    Week 160
    17.5
    26.9%
    18.5
    28.5%
    14.5
    21.3%
    Week 172
    17.5
    26.9%
    14.8
    22.8%
    14.5
    21.3%
    Week 184
    17.5
    26.9%
    18.5
    28.5%
    6.5
    9.6%
    Week 196
    15.8
    24.3%
    13.0
    20%
    12.9
    19%
    Week 208
    17.5
    26.9%
    13.0
    20%
    9.7
    14.3%
    Week 220
    15.8
    24.3%
    11.1
    17.1%
    9.7
    14.3%
    Week 232
    15.8
    24.3%
    3.7
    5.7%
    8.1
    11.9%
    Week 244
    12.3
    18.9%
    5.6
    8.6%
    8.1
    11.9%
    Week 256
    12.3
    18.9%
    3.7
    5.7%
    4.8
    7.1%
    Week 268
    3.5
    5.4%
    3.7
    5.7%
    1.6
    2.4%
    7. Secondary Outcome
    Title Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)
    Description
    Time Frame CORE baseline up to approximately 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Number analyzed is based on available data at specific visits
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
    Measure Participants 57 54
    Week 12 - CORE
    -0.8
    (29.77)
    -6.4
    (14.35)
    Week 24 - CORE
    -0.6
    (32.38)
    -7.2
    (15.19)
    8. Secondary Outcome
    Title Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
    Description Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm.
    Time Frame CORE and extension baseline up to approximately 268 weeks

    Outcome Measure Data

    Analysis Population Description
    Available data for analysis differed from visit to visit
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16 - extension
    -7.9
    (24.90)
    -6.9
    (14.88)
    -8.4
    (49.64)
    Week 28 - extension
    -9.0
    (24.21)
    -4.5
    (4.12)
    -3.0
    (3.86)
    Week 40 - extension
    -9.7
    (25.40)
    -5.8
    (13.93)
    -11.2
    (58.28)
    Week 52 - extension
    -10.7
    (26.60)
    -7.1
    (17.08)
    -2.5
    (3.02)
    Week 64 - extension
    -11.3
    (28.37)
    -7.9
    (17.30)
    -15.7
    (76.06)
    Week 76 - extension
    -5.5
    (5.96)
    -7.2
    (16.16)
    -3.5
    (4.27)
    Week 88 - extension
    -5.7
    (6.21)
    -6.2
    (8.55)
    -3.6
    (3.22)
    Week 100 - extension
    -5.6
    (5.71)
    -5.3
    (5.06)
    -3.8
    (4.28)
    Week 112 - extension
    -5.8
    (6.03)
    -4.4
    (6.57)
    -3.9
    (5.13)
    Week 124 - extension
    -5.5
    (5.85)
    -6.0
    (6.26)
    -4.0
    (4.36)
    Week 136 - extension
    -6.0
    (6.59)
    -5.3
    (4.99)
    -4.0
    (4.44)
    Week 148 - extension
    -6.3
    (6.21)
    6.1
    (6.28)
    -3.8
    (3.11)
    Week 160 - extension
    -5.5
    (4.70)
    -4.9
    (5.33)
    -3.2
    (2.25)
    Week 172 - extension
    -6.3
    (6.34)
    -5.9
    (5.97)
    -3.0
    (2.47)
    Week 184 - extension
    -6.3
    (5.44)
    -5.8
    (5.79)
    -3.3
    (2.31)
    Week 196 - extension
    -7.1
    (6.81)
    -6.5
    (7.17)
    -3.4
    (2.71)
    Week 208 - extension (n=22,20,23)
    -7.0
    (6.82)
    -6.2
    (6.22)
    -3.5
    (2.50)
    Week 220 - extension
    -7.1
    (6.91)
    -7.1
    (8.12)
    -3.8
    (2.48)
    Week 232 - extension
    -5.7
    (5.46)
    -6.8
    (8.10)
    -4.2
    (2.46)
    Week 244 - extension
    -6.0
    (6.03)
    -2.4
    (0.90)
    -4.2
    (2.58)
    Week 256 - extension
    -6.4
    (5.91)
    -4.9
    (3.49)
    -5.0
    (3.26)
    Week 268 - extension
    -3.6
    (1.58)
    -2.5
    (0.57)
    -3.7
    (2.23)
    9. Secondary Outcome
    Title Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)
    Description Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range
    Time Frame CORE baseline up to approximately 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Available data for analysis varies from visit to visit
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
    Measure Participants 57 54
    CORE Week 12
    0.7
    (0.97)
    -1.1
    (1.03)
    CORE Week 24
    -0.7
    (0.97)
    -1.1
    (1.12)
    10. Secondary Outcome
    Title Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
    Description Change from CORE baseline at each scheduled assessment was performed for patients randomized to pasireotide arms. Change from extension baseline at each scheduled assessment was performed for patients randomized to active control arm. Standardized IGF-1 = IGF-1 value / ULN, where ULN is the upper limit of the normal range
    Time Frame CORE and extension baseline up to approximately 268 weeks

    Outcome Measure Data

    Analysis Population Description
    Available data for analysis differed from visit to visit
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16 extension
    -0.8
    (0.99)
    -1.4
    (0.97)
    -0.9
    (0.81)
    Week 28 extension
    -0.9
    (1.00)
    -1.3
    (1.13)
    -0.9
    (0.88)
    Week 40 extension
    -1.1
    (0.95)
    -1.4
    (0.94)
    -1.1
    (0.91)
    Week 52 extension
    -1.1
    (0.90)
    -1.3
    (0.95)
    -1.1
    (0.95)
    Week 64 extension
    -1.3
    (0.99)
    -1.4
    (0.98)
    -1.3
    (0.81)
    Week 76 extension
    -1.3
    (0.87)
    -1.5
    (0.94)
    -1.3
    (0.84)
    Week 88 extension
    -1.3
    (0.80)
    -1.6
    (1.01)
    -1.3
    (0.90)
    Week 100 extension
    -1.4
    (0.93)
    -1.5
    (0.95)
    -1.3
    (0.92)
    Week 112 extension
    -1.5
    (0.87)
    -1.5
    (1.00)
    -1.4
    (0.89)
    Week 124 extension
    -1.4
    (0.86)
    -1.5
    (0.95)
    -1.3
    (0.97)
    Week 136 extension
    -1.4
    (0.91)
    -1.7
    (0.92)
    -1.4
    (0.86)
    Week 148 extension
    -1.4
    (0.86)
    -1.5
    (0.99)
    -1.3
    (0.84)
    Week 160 extension
    -1.4
    (0.90)
    -1.6
    (0.87)
    -1.4
    (0.94)
    Week 172 extension
    -1.5
    (0.81)
    -1.6
    (0.97)
    -1.3
    (0.98)
    Week 184 extension
    -1.3
    (0.70)
    -1.5
    (1.03)
    -1.4
    (0.93)
    Week 196 extension
    -1.4
    (0.81)
    -1.5
    (1.11)
    -1.3
    (1.11)
    Week 208 extension
    -1.4
    (0.79)
    -1.6
    (1.00)
    -1.2
    (0.98)
    Week 220 extension
    -1.4
    (0.94)
    -1.6
    (1.06)
    -1.4
    (0.91)
    Week 232 extension
    -1.4
    (0.92)
    -1.5
    (1.13)
    -1.7
    (0.82)
    Week 244 extension
    -1.3
    (0.75)
    -1.9
    (1.12)
    -1.5
    (0.79)
    Week 256 extension
    -1.3
    (0.58)
    -1.4
    (1.39)
    -1.8
    (0.90)
    Week 268 extension
    -1.4
    (0.43)
    -1.7
    (0.39)
    -1.7
    (0.81)
    11. Secondary Outcome
    Title Duration of the First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)
    Description n is the number of patients achieving response criteria. The weeks correspond to duration of first response (in weeks) for patients achieving biomedical control. Median and 95% CI are derived from Kaplan-Meier curves. Kaplan-Meier estimates [95% CI] at each time point are estimates of probability of response.
    Time Frame CORE baseline up to approximately 268 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Median (95% Confidence Interval) [weeks]
    29.1
    26.9
    24.9
    12. Secondary Outcome
    Title Time to First Response (Weeks) by Treatment for Patients Achieving a Reduction of Mean GH Level to < 2.5 µg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly
    Description Time to first response is defined as the time from the date of first dose to the date of first occurrence of a reduction of mean GH < 2.5 µg/L and the normalization of IGF-1. The weeks correspond to time taken to achieve first mean GH < 2.5 µg/L and the normalization of IGF-1.
    Time Frame CORE baseline up to approximately 268 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Median (95% Confidence Interval) [weeks]
    112.3
    65.3
    95.1
    13. Secondary Outcome
    Title Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set)
    Description Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid.
    Time Frame CORE baseline up to approximately 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Available data available for analysis differed from visit to visit
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
    Measure Participants 57 54
    Week 4 CORE
    3.5
    (11.28)
    2.3
    (11.08)
    Week 8 CORE
    2.4
    (12.97)
    2.5
    (12.11)
    Week 12 CORE
    3.0
    (12.41)
    1.9
    (11.50)
    Week 16 CORE
    3.3
    (12.99)
    6.6
    (15.33)
    Week 20 CORE
    3.5
    (12.89)
    4.0
    (16.02)
    Week24 CORE
    3.0
    (16.61)
    5.4
    (17.77)
    14. Secondary Outcome
    Title Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)
    Description Acromegaly Quality of Life questionnaire (AcroQoL) is a validated disease specific questionnaire. It contains 22 items divided into two scales: physical aspects (8 items) and psychological aspects (14 items) which is divided in two sub-scales: physical appearance and personal relationships of the patient (seven items each). The total score and sub-scores were calculated using the following formula: ((X -Y) / 4Y) x 100, X=sum of the scores for individual items (between 1 and 5 for each item), Y=number of individual items included in above sum (i.e. 22 for the total score, 8 for the physical sub-score, 14 for the psychological sub-score, 7 for the sub-score 'appearance' and 'personal relations'). The scoring of the questionnaire was performed as specified by the instrument developers. Total scores range from 0 to 100. Higher scores represent better quality of life. If more than 25% of items are not completed, results were considered invalid.
    Time Frame CORE Baseline and extension baseline up to approximately 268 weeks

    Outcome Measure Data

    Analysis Population Description
    completed and valid questionnaires at visits
    Arm/Group Title Pasireotide LAR 40 mg Extension Pasireotide LAR 60 mg Extension Cross Over to Pasireotide Extension
    Arm/Group Description If controlled on 40 mg in CORE, remain on blinded 40 mg in extension. If patient became uncontrolled, switch to open label 60 mg If controlled on 60 mg in CORE, remain on blinded 60 mg in extension. If patient became uncontrolled, switch to open label 60 mg Open - label 60 mg pasireotide. Control group from CORE discontinued study if controlled in CORE. If uncontrolled in CORE, switched to open label 60 mg pasireotide. Extension blinded 40 and 60 mg switched to open label if became uncontrolled.
    Measure Participants 57 54 62
    Week 16 extension
    4.2
    (16.34)
    2.9
    (19.09)
    0.8
    (10.22)
    Week 28 extension
    5.6
    (13.21)
    4.8
    (16.83)
    3.3
    (10.70)
    Week 40 extension
    3.2
    (15.78)
    2.5
    (18.21)
    3.2
    (10.31)
    Week 52 extension
    6.1
    (14.28)
    5.7
    (18.69)
    4.2
    (11.01)
    Week 64 extension
    5.8
    (13.65)
    4.2
    (18.89)
    5.4
    (12.12)
    Week 76 extension
    7.7
    (14.93)
    2.5
    (19.30)
    7.7
    (15.17)
    Week 88 extension
    4.6
    (15.11)
    5.6
    (18.08)
    6.4
    (10.29)
    Week 100 extension
    4.3
    (14.80)
    3.9
    (16.91)
    5.9
    (11.13)
    Week 112 extension
    4.6
    (15.83)
    6.5
    (18.36)
    4.1
    (10.35)
    Week 124 extension
    5.8
    (16.46)
    2.0
    (17.95)
    2.0
    (10.97)
    Week 136 extension
    7.5
    (18.72)
    5.4
    (16.73)
    6.5
    (11.82)
    Week 148 extension
    7.6
    (18.56)
    6.8
    (16.65)
    5.5
    (12.95)
    Week 160 extension
    7.0
    (19.10)
    5.1
    (15.70)
    1.5
    (13.36)
    Week 172 extension
    4.8
    (17.97)
    5.7
    (17.52)
    2.1
    (12.13)
    Week 184 extension
    5.8
    (15.31)
    5.8
    (16.83)
    1.6
    (12.45)
    Week 196 extension
    6.1
    (16.94)
    6.0
    (18.58)
    3.8
    (13.11)
    Week 208 extension
    1.2
    (13.27)
    6.2
    (17.31)
    4.5
    (12.62)
    Week 220 extension
    4.8
    (21.99)
    5.8
    (17.12)
    7.3
    (16.28)
    Week 232 extension
    2.1
    (17.51)
    -0.2
    (16.73)
    7.0
    (15.15)
    Week 244 extension
    4.5
    (20.06)
    6.3
    (11.05)
    3.0
    (18.65)
    Week 256 extension
    6.1
    (25.91)
    -3.0
    (7.07)
    0.3
    (14.08)
    Week 268 extension
    0.6
    (16.74)
    -4.9
    (4.30)
    -10.6
    (7.57)
    15. Secondary Outcome
    Title Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set)
    Description PK samples were collected for those patients treated with pasireotide LAR in the core study and who continued on pasireotide LAR in the extension phase. PK samples were collected before the injection of pasireotide LAR only at weeks 112 and 196. PK samples were also collected at weeks 48 and 132 only for all patients treated with octreotide LAR 30 mg or lanreotide ATG 120 mg in the core study who started treatment with pasireotide LAR in the extension study. Blood samples (2.5 mL each sample) were collected to yield 1-mL plasma for analysis of pasireotide LAR oncentration.
    Time Frame Extension baseline up to approximately 196 weeks

    Outcome Measure Data

    Analysis Population Description
    Available data for analysis varies at visits
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg
    Arm/Group Description Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
    Measure Participants 116 93
    Week 48
    5.70
    (3.159)
    Week 112
    8.66
    (4.154)
    14.06
    (9.807)
    Week 132
    9.28
    (5.067)
    Week 196
    10.32
    (5.473)
    14.96
    (10.210)

    Adverse Events

    Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 268 weeks
    Adverse Event Reporting Description Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator. The adverse events were reported on the combined CORE and extension and there were 5 patients who never received drug and 1 with no post baseline safety assessment.
    Arm/Group Title Pasireotide LAR 40 mg Pasireotide LAR 60 mg Cross-over to Pasireotide
    Arm/Group Description Pasireotide LAR 40 mg Pasireotide LAR 60 mg Cross-over to pasireotide
    All Cause Mortality
    Pasireotide LAR 40 mg Pasireotide LAR 60 mg Cross-over to Pasireotide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/63 (3.2%) 0/62 (0%) 0/62 (0%)
    Serious Adverse Events
    Pasireotide LAR 40 mg Pasireotide LAR 60 mg Cross-over to Pasireotide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 18/63 (28.6%) 14/62 (22.6%) 20/62 (32.3%)
    Blood and lymphatic system disorders
    Anaemia 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Cardiac disorders
    Atrial flutter 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Tachycardia 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Ventricular extrasystoles 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Congenital, familial and genetic disorders
    Cowden's disease 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Ear and labyrinth disorders
    Inner ear disorder 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Vertigo 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Endocrine disorders
    Thyroid mass 0/63 (0%) 0/62 (0%) 2/62 (3.2%)
    Gastrointestinal disorders
    Abdominal pain 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Gastrointestinal haemorrhage 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Haemorrhoids 1/63 (1.6%) 0/62 (0%) 1/62 (1.6%)
    Inguinal hernia 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Nausea 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    General disorders
    Death 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Drug ineffective 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Pyrexia 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Cholecystitis 1/63 (1.6%) 1/62 (1.6%) 1/62 (1.6%)
    Cholecystitis acute 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Cholecystitis chronic 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Cholelithiasis 3/63 (4.8%) 1/62 (1.6%) 3/62 (4.8%)
    Gallbladder polyp 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Infections and infestations
    Abdominal abscess 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Arthritis bacterial 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Erysipelas 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Flavivirus infection 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Gastroenteritis 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Herpes zoster 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Liver abscess 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Pneumonia 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Staphylococcal infection 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Subcutaneous abscess 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Urinary tract infection 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Injury, poisoning and procedural complications
    Drug administration error 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Joint dislocation 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Pneumocephalus 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Investigations
    Blood glucose increased 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    C-reactive protein increased 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Electrocardiogram ST segment elevation 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Metabolism and nutrition disorders
    Diabetes mellitus 0/63 (0%) 0/62 (0%) 2/62 (3.2%)
    Diabetic metabolic decompensation 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Hyperglycaemia 1/63 (1.6%) 1/62 (1.6%) 1/62 (1.6%)
    Hypoglycaemia unawareness 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Hyponatraemia 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/63 (1.6%) 1/62 (1.6%) 1/62 (1.6%)
    Musculoskeletal pain 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Osteitis 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Lung neoplasm malignant 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Metastases to spine 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Pituitary tumour 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Pituitary tumour benign 0/63 (0%) 1/62 (1.6%) 1/62 (1.6%)
    Uterine leiomyoma 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Nervous system disorders
    Brain oedema 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Cerebrospinal fluid leakage 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Dizziness 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Intracranial aneurysm 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Metabolic encephalopathy 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Nerve compression 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Transient ischaemic attack 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Pregnancy 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Psychiatric disorders
    Suicide attempt 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/63 (1.6%) 1/62 (1.6%) 0/62 (0%)
    Glomerulonephritis 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Renal colic 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Renal cyst 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Reproductive system and breast disorders
    Dysfunctional uterine bleeding 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Ovarian cyst 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Ovarian cyst ruptured 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Epistaxis 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Pulmonary embolism 0/63 (0%) 1/62 (1.6%) 1/62 (1.6%)
    Surgical and medical procedures
    Joint arthroplasty 0/63 (0%) 1/62 (1.6%) 0/62 (0%)
    Maxillofacial operation 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Oral surgery 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Vascular disorders
    Deep vein thrombosis 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Haematoma 0/63 (0%) 0/62 (0%) 1/62 (1.6%)
    Hypovolaemic shock 1/63 (1.6%) 0/62 (0%) 0/62 (0%)
    Other (Not Including Serious) Adverse Events
    Pasireotide LAR 40 mg Pasireotide LAR 60 mg Cross-over to Pasireotide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 59/63 (93.7%) 58/62 (93.5%) 61/62 (98.4%)
    Blood and lymphatic system disorders
    Anaemia 9/63 (14.3%) 10/62 (16.1%) 16/62 (25.8%)
    Leukopenia 0/63 (0%) 2/62 (3.2%) 4/62 (6.5%)
    Cardiac disorders
    Atrioventricular block first degree 6/63 (9.5%) 2/62 (3.2%) 2/62 (3.2%)
    Gastrointestinal disorders
    Abdominal pain 10/63 (15.9%) 10/62 (16.1%) 6/62 (9.7%)
    Abdominal pain upper 6/63 (9.5%) 3/62 (4.8%) 1/62 (1.6%)
    Constipation 5/63 (7.9%) 3/62 (4.8%) 3/62 (4.8%)
    Diarrhoea 14/63 (22.2%) 17/62 (27.4%) 11/62 (17.7%)
    Large intestine polyp 2/63 (3.2%) 1/62 (1.6%) 4/62 (6.5%)
    Nausea 7/63 (11.1%) 7/62 (11.3%) 3/62 (4.8%)
    Vomiting 8/63 (12.7%) 1/62 (1.6%) 0/62 (0%)
    General disorders
    Asthenia 1/63 (1.6%) 5/62 (8.1%) 5/62 (8.1%)
    Fatigue 4/63 (6.3%) 4/62 (6.5%) 2/62 (3.2%)
    Pyrexia 7/63 (11.1%) 1/62 (1.6%) 2/62 (3.2%)
    Hepatobiliary disorders
    Biliary dilatation 3/63 (4.8%) 3/62 (4.8%) 4/62 (6.5%)
    Cholelithiasis 21/63 (33.3%) 20/62 (32.3%) 17/62 (27.4%)
    Gallbladder polyp 4/63 (6.3%) 3/62 (4.8%) 1/62 (1.6%)
    Hepatic steatosis 4/63 (6.3%) 4/62 (6.5%) 2/62 (3.2%)
    Infections and infestations
    Gastroenteritis 2/63 (3.2%) 6/62 (9.7%) 0/62 (0%)
    Influenza 9/63 (14.3%) 9/62 (14.5%) 5/62 (8.1%)
    Upper respiratory tract infection 4/63 (6.3%) 3/62 (4.8%) 1/62 (1.6%)
    Urinary tract infection 6/63 (9.5%) 5/62 (8.1%) 9/62 (14.5%)
    Viral upper respiratory tract infection 7/63 (11.1%) 9/62 (14.5%) 5/62 (8.1%)
    Injury, poisoning and procedural complications
    Fall 0/63 (0%) 4/62 (6.5%) 1/62 (1.6%)
    Investigations
    Blood creatine phosphokinase increased 2/63 (3.2%) 1/62 (1.6%) 6/62 (9.7%)
    Blood glucose increased 3/63 (4.8%) 6/62 (9.7%) 0/62 (0%)
    Insulin-like growth factor decreased 2/63 (3.2%) 4/62 (6.5%) 2/62 (3.2%)
    Lipase increased 4/63 (6.3%) 1/62 (1.6%) 4/62 (6.5%)
    Weight increased 1/63 (1.6%) 0/62 (0%) 5/62 (8.1%)
    Metabolism and nutrition disorders
    Diabetes mellitus 20/63 (31.7%) 25/62 (40.3%) 16/62 (25.8%)
    Dyslipidaemia 4/63 (6.3%) 1/62 (1.6%) 3/62 (4.8%)
    Hypercholesterolaemia 5/63 (7.9%) 6/62 (9.7%) 8/62 (12.9%)
    Hyperglycaemia 25/63 (39.7%) 24/62 (38.7%) 15/62 (24.2%)
    Hypertriglyceridaemia 1/63 (1.6%) 4/62 (6.5%) 1/62 (1.6%)
    Hypoglycaemia 7/63 (11.1%) 7/62 (11.3%) 4/62 (6.5%)
    Hypomagnesaemia 4/63 (6.3%) 2/62 (3.2%) 0/62 (0%)
    Type 2 diabetes mellitus 1/63 (1.6%) 3/62 (4.8%) 4/62 (6.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/63 (11.1%) 9/62 (14.5%) 3/62 (4.8%)
    Back pain 13/63 (20.6%) 7/62 (11.3%) 3/62 (4.8%)
    Musculoskeletal pain 0/63 (0%) 4/62 (6.5%) 1/62 (1.6%)
    Pain in extremity 4/63 (6.3%) 2/62 (3.2%) 4/62 (6.5%)
    Nervous system disorders
    Dizziness 8/63 (12.7%) 3/62 (4.8%) 3/62 (4.8%)
    Headache 18/63 (28.6%) 6/62 (9.7%) 8/62 (12.9%)
    Psychiatric disorders
    Anxiety 5/63 (7.9%) 3/62 (4.8%) 2/62 (3.2%)
    Renal and urinary disorders
    Haematuria 7/63 (11.1%) 2/62 (3.2%) 0/62 (0%)
    Renal cyst 3/63 (4.8%) 5/62 (8.1%) 2/62 (3.2%)
    Skin and subcutaneous tissue disorders
    Alopecia 3/63 (4.8%) 8/62 (12.9%) 2/62 (3.2%)
    Vascular disorders
    Hypertension 7/63 (11.1%) 4/62 (6.5%) 5/62 (8.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01137682
    Other Study ID Numbers:
    • CSOM230C2402
    • EUDRACT 2009-016722-13
    First Posted:
    Jun 4, 2010
    Last Update Posted:
    Apr 5, 2018
    Last Verified:
    Apr 1, 2018