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Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's Disease

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ClinicalTrials.gov Identifier: NCT01374906
Recruitment Status : Completed
First Posted : June 16, 2011
Results First Posted : April 11, 2018
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cushing's Disease
Interventions Drug: pasireotide LAR
Drug: SOM230 LAR 30 mg
Drug: SOM230 LAR 10 mg
Enrollment 150
Recruitment Details At least 148 patients (Pts.) were planned & 150 were randomized & analyzed. Pts. were all treated with either pasireotide long-acting 10 mg or pasireotide long-acting 30 mg. 81 Pts. completed the Core phase & entered the Extension phase with 39 completing the Extension phase.
Pre-assignment Details  
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Period Title: Overall Study
Started 74 76
DC Dur Core Phs at/Prior to Data Cutoff 24 22
Completed Core Phase 50 54
Completed Core/Did Not Enter Ext. Phase 10 13
Completed Core Phase/Entered Ext. Phase 40 41
DC Dur Ext Phs at/Prior to Data Cutoff 16 26
Completed Extension Phase 24 15
Completed 34 28
Not Completed 40 48
Reason Not Completed
Abnormal laboratory value(s)             0             3
Administrative problems             2             2
Adverse Event             10             11
Death             0             2
Protocol Violation             2             2
Withdrawal by Subject             15             9
Unsatisfactory therapeutic effect             11             19
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose Total
Hide Arm/Group Description Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. Total of all reporting groups
Overall Number of Baseline Participants 74 76 150
Hide Baseline Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 74 participants 76 participants 150 participants
38.3  (12.52) 38.6  (12.99) 38.5  (12.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 76 participants 150 participants
Female
58
  78.4%
60
  78.9%
118
  78.7%
Male
16
  21.6%
16
  21.1%
32
  21.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 74 participants 76 participants 150 participants
Caucasian 39 44 83
Asian 27 24 51
Black 2 0 2
Other 6 8 14
1.Primary Outcome
Title Percentage Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 Regardless of Dose Titration
Hide Description Percentage of participants that attained a mean urinary free cortisol (mUFC) <= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.9
(30.51 to 53.94)
40.8
(29.65 to 52.67)
2.Secondary Outcome
Title Percentage of Participants That Attained a mUFC ≤ 1.0 x ULN at Month 7 and Had Not Had a Dose Increase at Month 4
Hide Description

Percentage of participants that attain a mUFC ≤ 1.0×ULN at Month 7 and had not had a dose increase at Month 4. Patients who had a dose increase prior to Month 7 were counted as non-responders in this analysis.

Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.

A responder was defined as a patient who attains mUFC ≤1.0 X ULN and had not had a dose increase at Month 4.

Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.4
(18.50 to 40.05)
31.6
(21.39 to 43.25)
3.Secondary Outcome
Title Actual Change in Mean Urinary Free Cortisol (mUFC) From Baseline
Hide Description Actual change in mUFC (nmol/24h) from baseline by randomized groups.
Time Frame baseline, Month 7 (M7), Month 12 (M12), Month 24 (M24) , Month 36 (M36)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: nmol/24h
M7 Number Analyzed 57 participants 67 participants
-192.4  (271.59) -234.3  (362.86)
M12 Number Analyzed 50 participants 54 participants
-195.1  (282.46) -247.6  (387.05)
M24 Number Analyzed 33 participants 25 participants
-236.2  (292.91) -265.2  (313.47)
M36 Number Analyzed 14 participants 4 participants
-398.4  (136.09) -164.6  (66.76)
4.Secondary Outcome
Title Percentage Change in Mean Urinary Free Cortisol (mUFC) From Baseline
Hide Description Percentage change in mUFC (nmol/24h) from baseline by randomized groups.
Time Frame M7, M12, M24, M36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: percentage change
M7 Number Analyzed 57 participants 67 participants
-29.3  (102.76) -33.2  (61.37)
M12 Number Analyzed 50 participants 54 participants
-30.3  (79.73) -31.1  (78.41)
M24 Number Analyzed 33 participants 25 participants
-50.9  (76.48) -51.2  (35.41)
M36 Number Analyzed 14 participants 4 participants
-71.6  (20.44) -48.8  (11.36)
5.Secondary Outcome
Title Percentage of Patients Who Attain mUFC ≤ 1.0 x ULN
Hide Description Controlled responder: mUFC ≤ 1.0×ULN by randomized groups.
Time Frame M7, M12, M24, M36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
M7 - Controlled responder Number Analyzed 74 participants 76 participants
39.2
(28.04 to 51.23)
40.8
(29.65 to 52.67)
M12 - Controlled responder Number Analyzed 74 participants 76 participants
35.1
(24.39 to 47.11)
25.0
(15.77 to 36.26)
M24 - Controlled responder Number Analyzed 63 participants 61 participants
39.7
(27.57 to 52.80)
21.3
(11.86 to 33.68)
M36 - Controlled responder Number Analyzed 50 participants 50 participants
22.0
(11.53 to 35.96)
4.0
(0.49 to 13.71)
6.Secondary Outcome
Title Percentage of Patients Who Attain mUFC ≤1.0 x ULN or Have at Least 50 % Reduction From Baseline in mUFC
Hide Description Controlled responder: mUFC ≤ 1.0×ULN. Partially controlled responder: at least 50% reduction in mUFC from Baseline, and mUFC >1.0×ULN.
Time Frame M7, M12, M24, M36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
M7 Number Analyzed 74 participants 76 participants
44.6
(33.02 to 56.61)
53.9
(42.13 to 65.45)
M12 Number Analyzed 74 participants 76 participants
45.9
(34.29 to 57.93)
42.1
(30.86 to 53.98)
M24 Number Analyzed 63 participants 61 participants
46.0
(33.39 to 59.06)
27.9
(17.15 to 40.83)
M36 Number Analyzed 50 participants 50 participants
28.0
(16.23 to 42.49)
6.0
(1.25 to 16.55)
7.Secondary Outcome
Title Percentage of Patients Who Are Controlled Responders (mUFC ≤ 1.0 xULN) on at Least 4 of the 7 mUFC Assessments by Month 7 & on at Least 7 of the 12 mUFC Assessments by Month 12.
Hide Description Percentage of patients with mUFC ≤ 1.0 x ULN at a minimum of 4 months up to and including Month 7, and at a minimum of 7 months up to and including Month 12 by randomized groups.
Time Frame Month 7, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 7
25.7
(16.22 to 37.16)
31.6
(21.39 to 43.25)
Month 12
25.7
(16.22 to 37.16)
25.0
(15.77 to 36.26)
8.Secondary Outcome
Title Percentage of Patients With Uncontrolled Response at Month 7 & Month 12 Within the Subset of Patients Who Had Uncontrolled Response at a) Months 1 and 2; b) Months 1, 2, and 3
Hide Description Percentage of patients with mUFC > 1.0 xULN at Month 7 and Month 12 within the subset of patients who were uncontrolled at a) Months 1 & 2, b) Months 1, 2, & 3 by randomized groups.
Time Frame Month 7, Month12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Unit of Measure: percentage of participants
Uncontrolled Resp @ M7: subset: M1 & 2 Number Analyzed 33 participants 33 participants
60.6 60.6
Uncontrolled Resp @ M7: subset: M1,2 & 3 Number Analyzed 31 participants 29 participants
61.3 65.5
Uncontrolled Resp @ M12: subset: M1 & 2 Number Analyzed 33 participants 33 participants
69.7 69.7
Uncontrolled Resp @ M12: subset: M1, 2 & 3 Number Analyzed 31 participants 29 participants
74.2 72.4
9.Secondary Outcome
Title Percent of Participants Attaining a mUFC ≤ 1.0 x ULN or at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points
Hide Description Time to first achievement of attaining a mUFC ≤ 1.0 x ULN or at least a 50% reduction in mUFC from baseline by randomized groups.
Time Frame Momth 7, Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Month 7
86.2
(76.1 to 93.5)
83.4
(72.6 to 91.8)
Month 12
90.1
(80.7 to 96.2)
94.5
(81.0 to 99.4)
10.Secondary Outcome
Title Percent of Participants Attaining a Duration of Controlled or Partially Controlled Response at Indicated Time Points
Hide Description Duration of controlled or partially controlled response is defined as the period starting from the date of patient’s first normalization (mUFC≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient’s mUFC >1.0 x ULN and the reduction from baseline falls to less than 50% for the first time.
Time Frame Month 6, 12, 18
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Month 6
78.0
(66.5 to 87.7)
72.9
(61.2 to 83.4)
Month 12
84.0
(73.1 to 92.2)
82.8
(71.5 to 91.5)
Month 18
84.0
(73.1 to 92.2)
87.1
(74.6 to 95.3)
11.Secondary Outcome
Title Percentage Change From Baseline on Plasma Adrenocorticotropic Hormone (ACTH) Over Time
Hide Description Percentage change in ACTH (pmol/L) from Baseline by randomized groups.
Time Frame Months 7, 12, 24 & 36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: Percentage change
M7 Number Analyzed 54 participants 62 participants
2.7  (57.14) -13.5  (46.75)
M12 Number Analyzed 44 participants 52 participants
-10.2  (57.57) -14.5  (38.72)
M24 Number Analyzed 31 participants 23 participants
-12.1  (43.51) 2.5  (68.69)
M36 Number Analyzed 13 participants 5 participants
-15.4  (36.90) -0.6  (48.13)
12.Secondary Outcome
Title Percentage Change From Baseline on Serum Cortisol Over Time
Hide Description Percentage change in serum cortisol (nmol/L) from Baseline by randomized groups.
Time Frame Months 7, 12, 24 & 36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: Percentage change
M7 Number Analyzed 55 participants 66 participants
-8.2  (37.83) -5.1  (40.20)
M12 Number Analyzed 46 participants 54 participants
-12.1  (29.69) -0.4  (35.91)
M24 Number Analyzed 32 participants 25 participants
-15.6  (30.67) -7.4  (38.37)
M36 Number Analyzed 14 participants 5 participants
0.6  (55.67) -23.2  (31.19)
13.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Blood Pressure
Hide Description Change in blood pressure measurements from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: mmHg
Supine systolic blood pressure (SBP) Number Analyzed 57 participants 67 participants
-6.8  (15.64) -4.6  (14.51)
Supine diastolic blood (DBP) pressure Number Analyzed 57 participants 67 participants
-4.8  (12.06) -3.0  (12.12)
14.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Body Mass Index (BMI)
Hide Description Change in BMI measurements from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: kg/m2
-0.7  (1.60) -1.8  (2.05)
15.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Weight
Hide Description Change in weight measurements from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: kg
-1.8  (4.16) -4.6  (5.08)
16.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Body Composition: Region
Hide Description Change in body composition: region measurements from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: percentage fat
-1.0  (2.64) -1.8  (3.97)
17.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Waist Circumference
Hide Description Change in waist circumference measurements from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: cm
-1.6  (8.47) -7.1  (11.78)
18.Secondary Outcome
Title Actual Change From Baseline in Clinical Signs Over Time: Cholesterol & Triglycerides
Hide Description Change in parameter measurements: cholesterol & triglycerides from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: mmol/L
Total cholesterol Number Analyzed 56 participants 64 participants
-0.5  (1.07) -0.4  (1.00)
HDL cholesterol Number Analyzed 55 participants 64 participants
-0.1  (0.28) 0  (0.32)
Triglycerides Number Analyzed 56 participants 64 participants
0  (0.53) -0.2  (0.64)
19.Secondary Outcome
Title Percentage Change From Baseline in Clinical Signs Over Time
Hide Description Percentage change in parameter measurements: blood pressure, body mass index, waist circumference, fasting serum lipid profile, weight, bone density and body composition (examined by DXA scan) from Baseline
Time Frame Month 7
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: Percentage change
SBP Number Analyzed 57 participants 67 participants
-4.3  (11.46) -3.0  (10.18)
DBP Number Analyzed 57 participants 67 participants
-4.7  (14.19) -2.6  (13.78)
BMI Number Analyzed 57 participants 67 participants
-2.6  (5.26) -6.1  (6.94)
Weight Number Analyzed 57 participants 67 participants
-2.6  (5.26) -6.1  (6.91)
Waist circumference Number Analyzed 53 participants 63 participants
-1.4  (8.60) -6.6  (10.06)
HDL Number Analyzed 55 participants 64 participants
-6.7  (15.18) 0.3  (20.91)
Total cholesterol Number Analyzed 56 participants 64 participants
-7.2  (16.86) -6.6  (16.40)
Triglycerides Number Analyzed 56 participants 64 participants
4.2  (39.54) -0.9  (39.61)
Body composition Number Analyzed 41 participants 48 participants
-2.4  (6.68) -3.6  (10.47)
20.Secondary Outcome
Title Percentage of Participants Having a Favorable Shift From Baseline in Clinical Signs
Hide Description This includes patients with improvements in symptoms from baseline. Clinical signs over time include: facial rubor, fat pads, hirsutism, striae, (via photographs by a second local physician who was blinded to the treatment dose and time point of the photograph) and muscle strength.
Time Frame Month 7
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Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Unit of Measure: Percentage of participants
Facial rubor Number Analyzed 52 participants 56 participants
32.7 53.6
Hirsutism (females only) Number Analyzed 42 participants 76 participants
22.2 32.6
Striae Number Analyzed 52 participants 55 participants
23.1 23.6
Bruising Number Analyzed 52 participants 56 participants
25.0 14.3
Supraclavicular fat pad Number Analyzed 52 participants 56 participants
40.4 28.6
Dorsal fat pad Number Analyzed 52 participants 55 participants
28.8 40.0
Muscle strength Number Analyzed 56 participants 66 participants
8.9 4.5
21.Secondary Outcome
Title Percentage of Participants That Attained a Mean Urinary Free Cortisol (mUFC) <= 1.0 x Upper Limit of Normal (ULN) at Month 7 Regardless of Dose Up-titration at Month 4.
Hide Description

All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.

Analysis split by screening strata of mUFC Stratum 1: mUFC 1.5x to < 2.0 x ULN Stratum 2: mUFC 2.0x to <= 5.0 x ULN

Time Frame Month 7
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Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
stratum:1.5 x ULN to < 2.0 x ULN Number Analyzed 25 participants 25 participants
52.0
(31.31 to 72.20)
52.0
(31.31 to 72.20)
stratum:2.0 x ULN to <= 5.0 x ULN Number Analyzed 49 participants 51 participants
36.7
(23.42 to 51.71)
35.3
(22.43 to 49.93)
22.Secondary Outcome
Title Percentage of Patients That Attain a Reduction of at Least 50% in mUFC From Baseline
Hide Description

All of the participants who discontinued prior to month 4 evaluations were classed as non-responders. For participants missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.

Analysis split by screening strata of mUFC

Stratum 1:

Time Frame Months 7, 12, 24 & 36
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
M7 Number Analyzed 74 participants 76 participants
35.1
(24.39 to 47.11)
43.4
(32.08 to 55.29)
M12 Number Analyzed 74 participants 76 participants
35.1
(24.39 to 47.11)
38.2
(27.25 to 50.02)
M24 Number Analyzed 24 participants 14 participants
83.3
(62.62 to 95.26)
57.1
(28.86 to 82.34)
M36 Number Analyzed 8 participants 3 participants
100
(63.06 to 100.00)
33.33
(0.84 to 90.57)
23.Secondary Outcome
Title Percent of Participants Attaining a Time to First Achievement of at Least a 50% Reduction in mUFC From Baseline at Indicated Time Points
Hide Description Time to first achievement of a 5by randomized groups.0% reduction in mUFC from baseline
Time Frame every month in the core phase and every 3 months in the extension phase) up to and including the cut-off date for the Month 12 CSR (10-Nov-2015)
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
M7
80.5
(69.7 to 89.3)
73.4
(62.4 to 83.4)
M12
84.4
(74.0 to 92.3)
80.7
(69.4 to 89.8)
24.Secondary Outcome
Title Percent of Participants With a Duration of at Least 50% Reduction in mUFC From Baseline at Indicated Time Points
Hide Description Duration of 50% reduction from baseline is defined as the period starting from the date of patient’s first 50% reduction from baseline
Time Frame Months 6, 12 & 18
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
M6
78.4
(66.6 to 88.3)
77.8
(66.0 to 87.7)
M12
84.9
(73.7 to 93.1)
83.7
(72.6 to 92.1)
M18
84.9
(73.7 to 93.1)
83.7
(72.6 to 92.1)
25.Secondary Outcome
Title Pharmacokinetic (PK) Parameter: Ctrough
Hide Description Pasireotide trough levels (Ctrough) was 1 of the parameters used for PK assessments. Ctrough is the pre-dose PK concentration with an elapsed time from previous injection of 28+/-2 days. All patients randomized to the study had at least 1 PK observation & were therefore included in the pharmacokinetic analysis set. PK observations with missing concentrations, missing dose, missing elapsed time or an elapsed time from previous injection outside of 28 ±2 days window were excluded. Given that SOM230 LAR was administered once a month, Ctrough was collected every 28 days and thus this provides a summary of Ctrough values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose & not an arm/group. Patients randomized to either 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.
Time Frame Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337
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Pharmacokinetic analysis set (PAS): The PAS consists of all randomized patients who have received at least one dose of study drug and had at least one post dosing PK assessment.

Patients were analyzed according to incident dose (defined as the last dose prior to the PK sample).

Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose 5 mg Pasireotide LAR Dose 40 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
These patients were dosed with 5 mg of Pasireotide LAR to assess Pharmacokinetics (PK).
These patients were dosed with 40 mg of Pasireotide LAR to assess Pharmacokinetics (PK).
Overall Number of Participants Analyzed 65 64 5 44
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 29 Number Analyzed 65 participants 64 participants 0 participants 0 participants
2.03  (1.25) 7.63  (4.58)
Day 57 Number Analyzed 57 participants 61 participants 1 participants 0 participants
2.35  (1.15) 7.82  (4.22) 0.83 [1]   (NA)
Day 85 Number Analyzed 59 participants 51 participants 2 participants 0 participants
2.39  (1.32) 8.56  (4.26) 1.03  (0.63)
Day 113 Number Analyzed 51 participants 49 participants 3 participants 0 participants
2.40  (1.11) 8.31  (3.87) 1.29  (0.24)
Day 141 Number Analyzed 25 participants 50 participants 2 participants 20 participants
2.47  (0.94) 7.88  (4.00) 1.04  (0.68) 10.7  (4.91)
Day 169 Number Analyzed 29 participants 51 participants 2 participants 22 participants
2.47  (0.95) 8.46  (3.51) 2.01  (0.22) 12.0  (5.08)
Day 197 Number Analyzed 35 participants 44 participants 2 participants 21 participants
2.88  (1.29) 9.13  (4.25) 0.72  (0.39) 11.9  (5.87)
Day 225 Number Analyzed 22 participants 28 participants 3 participants 34 participants
2.68  (0.98) 8.57  (4.70) 1.19  (0.43) 11.3  (5.18)
Day 253 Number Analyzed 17 participants 27 participants 5 participants 33 participants
2.87  (1.57) 9.00  (4.93) 1.77  (0.88) 12.1  (5.21)
Day 281 Number Analyzed 13 participants 16 participants 3 participants 44 participants
3.36  (1.48) 8.18  (4.23) 1.24  (0.52) 11.4  (5.85)
Day 309 Number Analyzed 23 participants 19 participants 1 participants 43 participants
2.50  (0.99) 9.34  (5.61) 0.66 [1]   (NA) 12.0  (4.58)
Day 337 Number Analyzed 21 participants 15 participants 3 participants 41 participants
3.07  (1.62) 8.90  (4.37) 1.91  (1.79) 12.6  (6.21)
[1]
N/A = not enough patients on this day to derive data
26.Secondary Outcome
Title Pharmacokinetic (PK) Parameter: Cmax
Hide Description Pasireotide peak levels (Cmax) was one of the parameters used for PK assessments. Cmax is the post-dose PK concentration with an elapsed time from the previous injection of 21+/-2 days. All patients randomized to the study had at least one PK observation and were therefore included in the pharmacokinetic analysis set (PAS). Cmax PK observations ("Day 20" and "Day 104") with an elapsed time from the previous injection outside of 21+/-2 days window were excluded. Given that SOM230 LAR was administered once a month, the Cmax were collected every 28 days in this study, thus this provides a summary of Cmax values provided by incident dose (last dose administered prior to PK sample collection), not by randomized dose, hence each column is equivalent to an incident dose and not an arm/group. Patients randomized to either the 10mg or 30mg could be titrated down to 5mg due to safety, or titrated up to 40mg, hence the 4 incident doses/columns that were allowed per protocol during this study.
Time Frame Days 22, 106, 190
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Hide Analysis Population Description

Pharmacokinetic analysis set (PAS): The PAS consists of all randomized patients who have received at least one dose of study drug and had at least one post dosing PK assessment.

Patients were analyzed according to incident dose (defined as the last dose prior to the PK sample).

Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose 5 mg Pasireptide LAR Dose 40 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
These patients were dosed with 5 mg of Pasireotide LAR to assess Pharmacokinetics (PK).
These patients were dosed with 40 mg of Pasireotide LAR to assess Pharmacokinetics (PK).
Overall Number of Participants Analyzed 67 69 3 22
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 22 (M 0.75) Number Analyzed 67 participants 69 participants 0 participants 0 participants
3.0  (1.50) 8.2  (3.99)
Day 106 (M 3.75) Number Analyzed 54 participants 51 participants 3 participants 0 participants
3.3  (1.92) 9.4  (3.72) 1.7  (0.42)
Day 190 (M6.75) Number Analyzed 32 participants 40 participants 2 participants 22 participants
4.0  (1.73) 10.0  (3.91) 1.4  (0.78) 12.1  (5.21)
27.Secondary Outcome
Title Actual Change in Standardized Score of Cushing’s Disease HRQoL (CushingQOL) Score From Baseline
Hide Description CushingQol is a disease-specific patient-reported outcome instrument. It is a single-domain 12 item Cushing's disease quality of life instrument. The Cushing’s syndrome quality of life (CushingQoL) questionnaire is a single domain questionnaire which includes 12 self-report items scored using a five point Likert scale anchored at (1=always/very much and 5=never/not at all). The patient is asked to report what they think or feel about their Cushing’s syndrome and how much the illness has interfered in usual activities over the past 4 weeks. The total score is standardized on a 0-100 scale with lower scores indicating a greater impact on quality of life.
Time Frame Months 7, 12, 24 & 36
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: scores on a scale
M7 Number Analyzed 56 participants 64 participants
5.7  (15.97) 7.8  (11.63)
M12 Number Analyzed 47 participants 53 participants
6.4  (17.56) 6.8  (14.42)
M24 Number Analyzed 32 participants 25 participants
5.9  (15.56) 8.7  (12.80)
M36 Number Analyzed 13 participants 4 participants
1.4  (9.10) 14.6  (5.10)
28.Secondary Outcome
Title Actual Change in SF-12v2 Score From Baseline - Mental Component Summary
Hide Description SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.
Time Frame Months 7, 12 & 24
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: scores on a scale
M7 Number Analyzed 33 participants 37 participants
4.1  (8.81) 4.3  (8.05)
M12 Number Analyzed 28 participants 33 participants
2.3  (9.97) 3.3  (8.26)
M24 Number Analyzed 9 participants 5 participants
3.3  (10.43) 6.4  (2.53)
29.Secondary Outcome
Title Actual Change in SF-12v2 Score From Baseline - Physical Component Summary
Hide Description SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.
Time Frame Months 7, 12 & 24
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Hide Analysis Population Description
Full analysis set (FAS): The FAS comprises all randomized patients who received at least one dose of study drug.
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose
Hide Arm/Group Description:
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR.
Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR.
Overall Number of Participants Analyzed 74 76
Mean (Standard Deviation)
Unit of Measure: scores on a scale
M7 Number Analyzed 33 participants 37 participants
1.9  (8.50) -0.8  (7.46)
M12 Number Analyzed 28 participants 33 participants
4.9  (5.56) -0.5  (6.73)
M24 Number Analyzed 9 participants 5 participants
5.3  (4.32) -1.1  (5.54)
Time Frame Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose All Patients
Hide Arm/Group Description Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 10 mg of Pasireotide LAR. Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. These patients were dosed with 30 mg of Pasireotide LAR. All Patients from both the 10 mg and 30 mg groups.
All-Cause Mortality
10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/74 (29.73%)   19/76 (25.00%)   41/150 (27.33%) 
Blood and lymphatic system disorders       
Anaemia  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Cardiac disorders       
Angina pectoris  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Angina unstable  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Cardiac arrest  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Cardiac failure  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Cardiopulmonary failure  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Coronary artery occlusion  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Sinus bradycardia  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Endocrine disorders       
Adrenal insufficiency  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Hyperadrenocorticism  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Pituitary-dependent Cushing's syndrome  1  2/74 (2.70%)  1/76 (1.32%)  3/150 (2.00%) 
Gastrointestinal disorders       
Anogenital dysplasia  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Gastric ulcer  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Haemorrhoids  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Large intestine polyp  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Oedematous pancreatitis  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
General disorders       
Injection site pain  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Malaise  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Hepatobiliary disorders       
Cholecystitis acute  1  2/74 (2.70%)  0/76 (0.00%)  2/150 (1.33%) 
Cholelithiasis  1  2/74 (2.70%)  3/76 (3.95%)  5/150 (3.33%) 
Infections and infestations       
Cellulitis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Diverticulitis  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Pneumonia  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Sepsis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Septic shock  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Subcutaneous abscess  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Injury, poisoning and procedural complications       
Femoral neck fracture  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Road traffic accident  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Stress fracture  1  2/74 (2.70%)  0/76 (0.00%)  2/150 (1.33%) 
Investigations       
Blood cortisol decreased  1  1/74 (1.35%)  1/76 (1.32%)  2/150 (1.33%) 
Blood cortisol increased  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Gamma-glutamyltransferase increased  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Metabolism and nutrition disorders       
Diabetes mellitus  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Hyperglycaemia  1  1/74 (1.35%)  1/76 (1.32%)  2/150 (1.33%) 
Musculoskeletal and connective tissue disorders       
Arthritis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Osteoarthritis  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Osteoporosis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Spondylolisthesis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Endometrial cancer  1  1/74 (1.35%)  1/76 (1.32%)  2/150 (1.33%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Renal and urinary disorders       
Acute kidney injury  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Nephrolithiasis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Reproductive system and breast disorders       
Endometrial hyperplasia  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Ovarian cyst  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Respiratory, thoracic and mediastinal disorders       
Dysphonia  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Dyspnoea  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Pulmonary artery thrombosis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Pulmonary embolism  1  0/74 (0.00%)  2/76 (2.63%)  2/150 (1.33%) 
Vascular disorders       
Deep vein thrombosis  1  0/74 (0.00%)  1/76 (1.32%)  1/150 (0.67%) 
Hypertensive crisis  1  1/74 (1.35%)  0/76 (0.00%)  1/150 (0.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
10 mg Pasireotide LAR Dose 30 mg Pasireotide LAR Dose All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   73/74 (98.65%)   76/76 (100.00%)   149/150 (99.33%) 
Blood and lymphatic system disorders       
Anaemia  1  4/74 (5.41%)  5/76 (6.58%)  9/150 (6.00%) 
Cardiac disorders       
Palpitations  1  4/74 (5.41%)  3/76 (3.95%)  7/150 (4.67%) 
Sinus bradycardia  1  4/74 (5.41%)  5/76 (6.58%)  9/150 (6.00%) 
Ear and labyrinth disorders       
Vertigo  1  5/74 (6.76%)  0/76 (0.00%)  5/150 (3.33%) 
Endocrine disorders       
Adrenal insufficiency  1  4/74 (5.41%)  6/76 (7.89%)  10/150 (6.67%) 
Hypothyroidism  1  1/74 (1.35%)  4/76 (5.26%)  5/150 (3.33%) 
Gastrointestinal disorders       
Abdominal discomfort  1  4/74 (5.41%)  2/76 (2.63%)  6/150 (4.00%) 
Abdominal distension  1  4/74 (5.41%)  5/76 (6.58%)  9/150 (6.00%) 
Abdominal pain  1  11/74 (14.86%)  13/76 (17.11%)  24/150 (16.00%) 
Abdominal pain upper  1  3/74 (4.05%)  8/76 (10.53%)  11/150 (7.33%) 
Constipation  1  5/74 (6.76%)  5/76 (6.58%)  10/150 (6.67%) 
Diarrhoea  1  26/74 (35.14%)  35/76 (46.05%)  61/150 (40.67%) 
Dry mouth  1  4/74 (5.41%)  1/76 (1.32%)  5/150 (3.33%) 
Flatulence  1  3/74 (4.05%)  5/76 (6.58%)  8/150 (5.33%) 
Frequent bowel movements  1  4/74 (5.41%)  0/76 (0.00%)  4/150 (2.67%) 
Nausea  1  17/74 (22.97%)  16/76 (21.05%)  33/150 (22.00%) 
Vomiting  1  7/74 (9.46%)  2/76 (2.63%)  9/150 (6.00%) 
General disorders       
Asthenia  1  10/74 (13.51%)  5/76 (6.58%)  15/150 (10.00%) 
Fatigue  1  13/74 (17.57%)  15/76 (19.74%)  28/150 (18.67%) 
Oedema peripheral  1  9/74 (12.16%)  12/76 (15.79%)  21/150 (14.00%) 
Pyrexia  1  5/74 (6.76%)  2/76 (2.63%)  7/150 (4.67%) 
Hepatobiliary disorders       
Cholelithiasis  1  15/74 (20.27%)  33/76 (43.42%)  48/150 (32.00%) 
Cholestasis  1  4/74 (5.41%)  2/76 (2.63%)  6/150 (4.00%) 
Gallbladder cholesterolosis  1  2/74 (2.70%)  4/76 (5.26%)  6/150 (4.00%) 
Hepatic function abnormal  1  2/74 (2.70%)  4/76 (5.26%)  6/150 (4.00%) 
Hepatic steatosis  1  1/74 (1.35%)  6/76 (7.89%)  7/150 (4.67%) 
Infections and infestations       
Bronchitis  1  5/74 (6.76%)  2/76 (2.63%)  7/150 (4.67%) 
Gastroenteritis  1  7/74 (9.46%)  2/76 (2.63%)  9/150 (6.00%) 
Influenza  1  12/74 (16.22%)  6/76 (7.89%)  18/150 (12.00%) 
Nasopharyngitis  1  18/74 (24.32%)  13/76 (17.11%)  31/150 (20.67%) 
Upper respiratory tract infection  1  5/74 (6.76%)  6/76 (7.89%)  11/150 (7.33%) 
Urinary tract infection  1  10/74 (13.51%)  9/76 (11.84%)  19/150 (12.67%) 
Injury, poisoning and procedural complications       
Contusion  1  4/74 (5.41%)  1/76 (1.32%)  5/150 (3.33%) 
Investigations       
Alanine aminotransferase increased  1  6/74 (8.11%)  5/76 (6.58%)  11/150 (7.33%) 
Blood cortisol decreased  1  4/74 (5.41%)  2/76 (2.63%)  6/150 (4.00%) 
Blood creatine phosphokinase increased  1  1/74 (1.35%)  6/76 (7.89%)  7/150 (4.67%) 
Blood glucose increased  1  6/74 (8.11%)  7/76 (9.21%)  13/150 (8.67%) 
Gamma-glutamyltransferase increased  1  7/74 (9.46%)  6/76 (7.89%)  13/150 (8.67%) 
Glycosylated haemoglobin increased  1  4/74 (5.41%)  4/76 (5.26%)  8/150 (5.33%) 
Lipase increased  1  2/74 (2.70%)  4/76 (5.26%)  6/150 (4.00%) 
Weight decreased  1  4/74 (5.41%)  3/76 (3.95%)  7/150 (4.67%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/74 (4.05%)  12/76 (15.79%)  15/150 (10.00%) 
Diabetes mellitus  1  15/74 (20.27%)  20/76 (26.32%)  35/150 (23.33%) 
Hypercholesterolaemia  1  3/74 (4.05%)  6/76 (7.89%)  9/150 (6.00%) 
Hyperglycaemia  1  36/74 (48.65%)  35/76 (46.05%)  71/150 (47.33%) 
Hyperlipidaemia  1  1/74 (1.35%)  4/76 (5.26%)  5/150 (3.33%) 
Hyperuricaemia  1  5/74 (6.76%)  5/76 (6.58%)  10/150 (6.67%) 
Hypoglycaemia  1  10/74 (13.51%)  12/76 (15.79%)  22/150 (14.67%) 
Type 2 diabetes mellitus  1  3/74 (4.05%)  4/76 (5.26%)  7/150 (4.67%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  9/74 (12.16%)  4/76 (5.26%)  13/150 (8.67%) 
Back pain  1  8/74 (10.81%)  8/76 (10.53%)  16/150 (10.67%) 
Muscle spasms  1  1/74 (1.35%)  5/76 (6.58%)  6/150 (4.00%) 
Musculoskeletal chest pain  1  0/74 (0.00%)  4/76 (5.26%)  4/150 (2.67%) 
Myalgia  1  4/74 (5.41%)  4/76 (5.26%)  8/150 (5.33%) 
Pain in extremity  1  6/74 (8.11%)  6/76 (7.89%)  12/150 (8.00%) 
Nervous system disorders       
Dizziness  1  10/74 (13.51%)  8/76 (10.53%)  18/150 (12.00%) 
Headache  1  18/74 (24.32%)  10/76 (13.16%)  28/150 (18.67%) 
Paraesthesia  1  1/74 (1.35%)  4/76 (5.26%)  5/150 (3.33%) 
Psychiatric disorders       
Insomnia  1  8/74 (10.81%)  5/76 (6.58%)  13/150 (8.67%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  2/74 (2.70%)  4/76 (5.26%)  6/150 (4.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  2/74 (2.70%)  5/76 (6.58%)  7/150 (4.67%) 
Dry skin  1  2/74 (2.70%)  5/76 (6.58%)  7/150 (4.67%) 
Erythema  1  2/74 (2.70%)  4/76 (5.26%)  6/150 (4.00%) 
Pruritus  1  5/74 (6.76%)  6/76 (7.89%)  11/150 (7.33%) 
Rash  1  4/74 (5.41%)  2/76 (2.63%)  6/150 (4.00%) 
Skin exfoliation  1  3/74 (4.05%)  4/76 (5.26%)  7/150 (4.67%) 
Vascular disorders       
Hypertension  1  11/74 (14.86%)  13/76 (17.11%)  24/150 (16.00%) 
Hypotension  1  4/74 (5.41%)  5/76 (6.58%)  9/150 (6.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.1)
All analyses in this study were descriptive in nature. No comparisons were made between the two arms, and no p-values are reported. For the primary and key-secondary, success was based on estimating the response rate (and 95% CI) in each arm.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01374906     History of Changes
Other Study ID Numbers: CSOM230G2304
2009-011128-70 ( EudraCT Number )
First Submitted: June 14, 2011
First Posted: June 16, 2011
Results First Submitted: December 11, 2017
Results First Posted: April 11, 2018
Last Update Posted: May 22, 2018