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Trial record 4 of 15 for:    "Acth-Secreting Pituitary Adenoma" | "Hydrocortisone acetate"

Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing's Disease

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ClinicalTrials.gov Identifier: NCT00434148
Recruitment Status : Completed
First Posted : February 12, 2007
Results First Posted : February 6, 2013
Last Update Posted : March 8, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cushing's Disease
Intervention Drug: Pasireotide
Enrollment 162
Recruitment Details The enrollment number reflects the participants who were randomized and received at least one dose of drug.
Pre-assignment Details A total of 165 participants were randomized, but 1 participant from the 600ug group and 2 participants from the 900ug group were not treated. Participants who completed month 12 and did not enter the extension phase were not counted as discontinuations.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Period Title: Overall Study
Started 82 [1] 80
Completed Month 12 39 39
Completed m. 12; Did Not Enter Extension 13 7
Completed Month 12; Entered Extension 26 32
Completed 13 7
Not Completed 69 73
Reason Not Completed
Adverse Event             18             18
Lack of Efficacy             25             28
Withdrawal by Subject             15             15
Protocol Violation             4             0
Administrative problems             6             10
Lost to Follow-up             0             1
Condition no longer requires study drug             1             0
Abnormal test procedure result             0             1
[1]
"Started" indicates Full Analysis Set. Patients randomized and treated.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug Total
Hide Arm/Group Description At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country. Total of all reporting groups
Overall Number of Baseline Participants 82 80 162
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 82 participants 80 participants 162 participants
40.5  (12.97) 39.9  (10.77) 40.2  (11.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 80 participants 162 participants
Female
62
  75.6%
64
  80.0%
126
  77.8%
Male
20
  24.4%
16
  20.0%
36
  22.2%
1.Primary Outcome
Title Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group
Hide Description A responder in the primary efficacy analysis was a patient with a mUFC≤ULN at Month 6 and whose dose was not increased prior to Month 6.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) was the primary population for efficacy and consisted of all 162 randomized patients who received at least one dose of paseriotide.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Responders
12
(7.0 to 22.3)
21
(16.6 to 35.9)
2.Secondary Outcome
Title Change From Baseline in mUFC
Hide Description Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement.
Time Frame baseline, 3 months, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: nmol/24h
month 3 (n=61,62) -375.8  (631.07) -343.4  (485.48)
month 12 (n=37,35) -572.6  (941.44) -350.7  (380.25)
3.Secondary Outcome
Title Time to First UFC Response
Hide Description Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Median (Inter-Quartile Range)
Unit of Measure: months
1.0
(0.9 to 2.7)
1.0
(0.9 to 2.7)
4.Secondary Outcome
Title Percent Change From Baseline in Serum Cortisol
Hide Description Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement.
Time Frame baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: Percent change
month 0.5 (n=77,76) -4.0  (28.23) -10.8  (30.57)
month 1 (n=78,72) -7.3  (30.13) -7.7  (32.00)
month 1.5 (n=75,71) -5.5  (27.65) -7.1  (31.34)
month 2 (n=73,67) -0.7  (35.81) -6.4  (29.75)
month 2.5 (n=70,67) -3.3  (31.40) -10.1  (31.23)
month 3 (n=70,67) -2.6  (35.79) -10.2  (25.60)
month 4 (n=68,61) -6.9  (31.88) -10.8  (28.10)
month 5 (n=62,58) -4.3  (36.96) -10.8  (26.50)
month 6 (n=59,57) -5.6  (34.28) -9.3  (31.45)
month 7 (n=52,53) -9.8  (34.44) -5.8  (26.35)
month 8 (n=50,46) -10.2  (30.85) -9.9  (35.79)
month 9 (n=46,48) -5.4  (33.49) -5.8  (31.56)
month 10 (n=42,47) -11.2  (30.25) -9.3  (28.39)
month 11 (n=41,41) -8.2  (38.19) -14.0  (29.63)
month 12 (n=39,38) -11.6  (33.75) -15.2  (21.99)
month 15 (n=26,26) -10.5  (30.14) -12.5  (29.27)
month 18 (n=26,25) -7.6  (40.35) -17.8  (28.39)
month 21 (n=21,25) -12.1  (34.23) -15.5  (34.94)
month 24 (n=18,22) -17.9  (43.46) -18.1  (34.27)
month 27 (n=16,18) -9.0  (41.71) -12.7  (28.53)
month 30 (n=14,19) -22.8  (35.43) -22.7  (32.46)
month 33 (n=13,15) -9.5  (44.64) -25.2  (25.96)
month 36 (n=10,13) -12.7  (65.43) -13.3  (37.84)
month 39 (n=10,12) -26.6  (42.89) -25.9  (33.15)
month 42 (n=10,12) -17.8  (39.54) -18.1  (35.25)
month 45 (n=10,11) -12.5  (44.89) -8.5  (32.55)
month 48 (n=9,11) -19.7  (37.88) -20.1  (39.42)
month 51 (n=9,9) -17.6  (34.60) -24.0  (31.53)
month 54 (n=9,9) -25.0  (30.49) -6.8  (28.07)
month 57 (n=8,8) -11.0  (56.61) -30.8  (22.21)
month 60 (n=8,8) -24.5  (31.89) -18.9  (22.05)
month 63 (n=6,7) -28.6  (31.20) -24.0  (26.41)
month 66 (n=4,6) -6.7  (29.29) -22.5  (36.19)
month 69 (n=3,5) -13.4  (42.68) -33.6  (10.31)
month 72 (n=3,4) -4.5  (40.94) -22.7  (23.57)
month 75 (n=2,3) -63.3  (41.13) -23.2  (25.71)
month 78 (n=1,1) 14.5 [1]   (NA) -53.3 [1]   (NA)
[1]
n=1; therefore, SD does not apply.
5.Secondary Outcome
Title Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)
Hide Description Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement.
Time Frame baseline, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: percent change
month 0.5 (n=78,75) 9.3  (181.17) -15.9  (30.75)
month 1 (n=78,71) -10.0  (37.29) -19.1  (30.47)
month 1.5 (n=74,69) -13.4  (31.64) -10.5  (38.05)
month 2 (n=72,66) -7.7  (40.86) -13.2  (35.38)
month 2.5 (n=69,65) -8.2  (37.32) -12.0  (47.02)
month 3 (n=69,66) -9.2  (40.85) -16.3  (31.93)
month 4 (n=66,61) -7.2  (38.42) -12.8  (44.06)
month 5 (n=62,55) -3.0  (42.50) -15.0  (38.89)
month 6 (n=58,55) -8.4  (43.61) -17.3  (35.60)
month 7 (n=52,52) -11.4  (45.25) -14.6  (30.88)
month 8 (n=48,46) -5.0  (51.75) -17.0  (36.87)
month 9 (n=46,47) -5.3  (55.27) -18.2  (35.87)
month 10 (n=42,46) -10.2  (48.82) -18.2  (34.18)
month 11 (n=42,40) -11.5  (44.52) -17.4  (39.06)
month 12 (n=39,39) -7.4  (53.83) -26.5  (33.38)
month 15 (n=26,26) -14.5  (43.44) -16.3  (32.01)
month 18 (n=26,25) -5.9  (57.56) -21.2  (32.91)
month 21 (n=20,23) -1.5  (51.52) -17.3  (34.34)
month 24 (n=18,21) -10.9  (47.95) -18.0  (26.53)
month 27 (n=16,18) -10.4  (53.33) -12.5  (39.39)
month 30 (n=14,18) -14.7  (56.17) -20.0  (40.82)
month 33 (n=13,14) -9.4  (55.01) -2.4  (33.07)
month 36 (n=10,13) 19.1  (112.26) 1.2  (35.33)
month 39 (n=10,12) -20.9  (48.68) -5.3  (40.02)
month 42 (n=10,12) -6.7  (59.61) 2.7  (42.35)
month 45 (n=9,11) 11.9  (89.59) 8.1  (50.09)
month 48 (n=9,9) -10.8  (65.52) 11.7  (55.85)
month 51 (n=9,9) 0.0  (65.82) -3.1  (48.21)
month 54 (n=9,9) 4.6  (77.49) 7.3  (52.94)
month 57 (n=7,7) 9.6  (59.86) -5.0  (45.19)
month 60 (n=8,8) 9.6  (61.38) -1.3  (39.01)
month 63 (n=6,7) 11.9  (73.78) 15.4  (50.66)
month 66 (n=4,6) 25.3  (75.31) 18.3  (61.35)
month 69 (n=3,5) 38.9  (78.34) -1.2  (23.98)
month 72 (n=3,3) 35.6  (78.48) 22.0  (46.15)
month 75 (n=2,3) -5.0  (77.78) 23.1  (110.92)
month 78 (n=1,1) 50.0 [1]   (NA) -11.1 [1]   (NA)
[1]
n=1; therefore, SD does not apply.
6.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)
Hide Description Sitting blood pressure assessments were performed at every study visit. A negative change from baseline indicates improvement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: mmHg
Sitting SBP, month 3 (n=70,67) -7.4  (17.37) -9.9  (17.01)
Sitting SBP, month 6 (n=59,57) -6.8  (19.35) -11.4  (15.92)
Sitting SBP, month 12 (n=39,39) -2.8  (18.40) -9.4  (14.61)
Sitting SBP, month 24 (n=18,23) -11.6  (12.82) -11.0  (11.58)
Sitting SBP, month 36 (n=10,13) -3.0  (17.08) -11.5  (16.23)
Sitting SBP, month 48 (n=9,10) -12.0  (14.15) -3.6  (14.56)
Sitting SBP, month 60 (n=7,8) -12.8  (17.10) -2.0  (11.83)
Sitting DBP, month 3 (n=70,67) -3.3  (11.01) -4.1  (13.11)
Sitting DBP , month 6 (n=59,57) -4.2  (13.54) -5.0  (11.56)
Sitting DBP, month 12 (n=39,39) -2.0  (11.65) -5.4  (10.86)
Sitting DBP, month 24 (n=18,23) -8.1  (11.35) -6.4  (9.37)
Sitting DBP, month 36 (n=10,13) -6.8  (14.17) -7.3  (8.25)
Sitting DBP, month 48 (n=9,10) -11.7  (12.02) -1.0  (9.30)
Sitting DBP, month 60 (n=7,8) -9.1  (9.79) 0.7  (7.34)
7.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)
Hide Description BMI was determined by using height and weight measurements. A negative change from baseline indicates improvement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: kg/m^2
month 3 (n=70,67) -1.0  (1.26) -1.4  (1.29)
month 6 (n=59,57) -1.2  (1.64) -2.1  (1.72)
month 12 (n=40,39) -2.1  (2.19) -2.8  (2.21)
month 24 (n=18,23) -3.4  (2.97) -3.0  (2.67)
month 36 (n=10,13) -2.9  (2.47) -3.3  (3.48)
month 48 (n=9,10) -3.1  (2.14) -2.4  (2.60)
month 60 (n=8,8) -2.8  (1.85) -2.0  (2.20)
8.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference
Hide Description Waist circumference was measured with a measuring tape correctly positioned. A negative change from baseline indicates improvement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: cm
month 3 (n=64,66) -1.0  (10.47) -2.2  (5.23)
month 6 (n=53,54) -1.9  (8.33) -3.4  (5.39)
month 12(n=34,35) -4.4  (9.40) -5.6  (7.86)
month 24 ( n=17,22) -8.7  (9.54) -5.1  (10.22)
month 36 (n=9,13) -7.8  (10.46) -6.4  (9.97)
month 48 (n=8,10) -8.3  (11.59) -5.1  (10.03)
month 60 (n=7,8) -7.3  (12.08) -4.6  (10.90)
9.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides
Hide Description Blood samples were drawn to obtain total cholesterol and triglycerides' levels. A negative change from baseline indicates improvement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: mmol/L
Cholesterol, month 3 (n=70,67) -0.2  (1.06) -0.3  (1.01)
Cholesterol, month 6 (n=59,55) -0.4  (1.24) -0.4  (0.98)
Cholesterol, month 12 (n=40,39) -0.5  (1.29) -0.6  (1.18)
Cholesterol, month 24 (n=18,22) -0.6  (1.39) -0.3  (0.81)
Cholesterol, month 36 (n=10,12) -0.8  (1.24) -0.1  (0.64)
Cholesterol, month 48 (n=9,10) -0.9  (1.63) -0.4  (0.80)
Cholesterol, month 60 (n=8,8) -1.5  (1.57) -0.4  (1.00)
Triglycerides, month 3 (n=70,67) 0.1  (1.07) 0.1  (1.01)
Triglycerides, month 6 (n=59,55) 0  (0.92) 0.1  (1.00)
Triglycerides, month 12 (n=40,39) -0.1  (0.77) -0.2  (0.69)
Triglycerides, month 24 (n=18,22) 0  (1.05) 0  (0.82)
Triglycerides, month 36 (n=10,12) -0.2  (0.99) 0.3  (1.38)
Triglycerides, month 48 (n=9,10) -0.5  (0.94) 0.4  (1.32)
Triglycerides, month 60 (n=8,8) -0.7  (1.01) 0.2  (1.02)
10.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score
Hide Description

The BDI-II is a 21 item self-report rating inventory measuring characteristic attitudes and symptoms of depression. The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The scores range as follows:

0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; and 29-63: severe depression. A negative change from baseline indicates imrpovement.

Time Frame baseline, month 3, month 6, month 12, month 18, month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: score on a scale
month 3 (n=66,65) -4.6  (8.29) -1.9  (9.88)
month 6 (n=56,55) -4.6  (9.49) -5.5  (8.81)
month 12 (n=38,37) -4.6  (9.19) -5.2  (9.94)
month 18 (n=6,6) -1.3  (5.24) -7.8  (5.78)
month 24 (n=0,1) NA [1]   (NA) -12.0 [2]   (NA)
[1]
No participants had month 24 values.
[2]
n=1; therefore, SD does not apply.
11.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score
Hide Description The Ferriman Gallwey scoring system is used to score the degree of excess male pattern body hair. The scorecard of every body location under survey begins from 0 (no excessive terminal hair growth) to 4 (extensive terminal hair growth) and the numbers are added up to a maximum count of 36. A score >= 6 indicates the hirsutism. A negative change from baseline indicates imrpovement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: score on a scale
month 3 (n=52,50) -1.3  (3.02) -1.3  (3.46)
month 6 (n=44,47) -0.9  (2.88) -2.4  (4.70)
month 12 (n=30,35) -1.3  (1.99) -3.5  (4.65)
month 24 (n=12,22) -2.8  (2.72) -4.0  (4.34)
month 36 (n=7,12) -3.7  (2.69) -3.2  (4.09)
month 48 (n=6,10) -6.0  (3.85) -2.5  (2.84)
month 60 (n=5,8) -5.0  (3.32) -2.9  (3.23)
12.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD)
Hide Description BMD was measured using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L1-L4), proximal femur (total hip) and proximal femur (femur neck). A negative change from baseline indicates imrpovement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: mg/cm^3
Lumbar vertebrae, month 3 (n=2,2) 0  (0.02) 0  (0)
Lumbar vertebrae, month 6 (n=47,39) 0  (0.06) 0  (0.04)
Lumbar vertebrae, month 12 (n=33,29) 0  (0.07) 0  (0.05)
Lumbar vertebrae, month 24 (n=16,16) 0  (0.04) 0  (0.05)
Lumbar vertebrae, month 36 (n=8,9) 0  (0.09) 0.1  (0.12)
Lumbar vertebrae, month 48 (n=9,8) 0  (0.12) 0  (0.05)
Lumbar vertebrae, month 60 (n=7,6) 0  (0.14) 0  (0.08)
Proximal femur (total hip), month 3 (2,2) 0  (0.04) 0  (0.01)
Proximal femur (total hip), month 6 (n=46,38) 0  (0.07) 0  (0.05)
Proximal femur (total hip), month 12 (n=33,26) 0  (0.04) 0  (0.03)
Proximal femur (total hip), month 24 (n=16,13) 0  (0.04) 0  (0.03)
Proximal femur (total hip), month 36 (n=8,8) 0  (0.03) 0  (0.06)
Proximal femur (total hip), month 48 (n=8,8) 0  (0.04) 0  (0.05)
Proximal femur (total hip), month 60 (n=7,6) -0.1  (0.14) 0  (0.06)
Proximal femur (femur neck), month 3 (n=2,2) 0  (0) 0  (0.03)
Proximal femur (femur neck), month 6 (n=46,38) 0  (0.03) 0  (0.05)
Proximal femur (femur neck), month 12 (n=33,28) 0  (0.04) 0  (0.07)
Proximal femur (femur neck), month 24 (n=16,14) 0  (0.05) 0  (0.04)
Proximal femur (femur neck), month 36 (n=8,8) 0  (0.02) 0  (0.04)
Proximal femur (femur neck), month 48 (n=9,7) 0  (0.05) 0  (0.04)
Proximal femur (femur neck), month 60 (7,6) 0  (0.10) 0  (0.05)
13.Secondary Outcome
Title Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition
Hide Description Body composition as in percentage of body fat by region was assessed by total body scan. A negative change from baseline indicates improvement.
Time Frame baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: Percentage of body fat
Month 3 (n=2,2) 2.9  (1.48) 0.3  (0.78)
Month 6 (n=39,32) -0.4  (3.77) -0.9  (4.06)
Month 12 (n=29,22) -3.0  (4.23) -1.6  (4.27)
Month 24 (n=13,14) -1.9  (3.24) -1.9  (5.70)
Month 36 (n=5,8) -2.0  (4.20) -1.1  (4.94)
Month 48 (n=4,7) -2.0  (5.07) 0.1  (5.63)
Month 60 (n=4,6) -2.8  (4.64) -0.5  (4.97)
14.Secondary Outcome
Title Change From Baseline in Tumor Volume
Hide Description Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement.
Time Frame baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: cm^3
month 6 (n=25, 28) 9.3  (44.02) -19.0  (36.82)
month 12 (n=15, 18) -8.1  (62.17) -43.8  (49.47)
month 18 (n=8, 11) -18.1  (71.62) -36.0  (65.42)
month 24 (n=7, 13) -27.4  (82.68) -11.5  (66.28)
month 30 (n=6, 8) -52.1  (55.20) -20.9  (77.16)
month 36 (n=3, 5) -94.1  (10.15) -27.6  (78.86)
month 42 (n=3, 3) -95.2  (8.40) 84.0  (282.60)
month 48 (n=3, 3) -20.5  (130.90) 29.2  (164.67)
month 54 (n=3, 2) -29.1  (107.40) 20.3  (170.15)
month 60 (n=3, 2) -13.5  (136.97) 127.6  (321.88)
month 66 (n= 1, 1) -100.0 [1]   (NA) 269.8 [1]   (NA)
month 72 (n=1, 0) 45.6 [1]   (NA) NA [2]   (NA)
month 78 (n=1, 0) 77.2 [1]   (NA) NA [3]   (NA)
[1]
n=1; therefore, SD does not apply.
[2]
No participants in this arm had month 72 values.
[3]
No participants in this arm had month 78 values.
15.Secondary Outcome
Title Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score
Hide Description A Cushing's syndrome health related quality of life (HRQL) questionnaire was completed. The Cushing’s Syndrome HRQL questionnaire contains 12 sentences with 5 possible answers each. The answers are based on Likert scales, with 5 response categories: Always, Often, Sometimes, Rarely and Never; or Very much, Quite a bit, Somewhat, Very little, and Not at all. The answers to each of the items are rated on a scale of 1 to 5. “1” corresponds to the response category “Always” or “Very much” and “5” corresponds to the category “Never” or “Not at all”. The score is the sum of all item responses and can range from 12 to 60 points. The lower the score, the greater the Cushing's Syndrome impacts on HRQoL. A positive change from baseline indicates improvement.
Time Frame baseline, 3 months, 6 months, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set, who had measurements at baseline and the post baseline time point, were included in the analysis for that post baseline time point. The full analysis set included all randomized participants who received at least one dose of study drug.
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description:
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country.
At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
Overall Number of Participants Analyzed 82 80
Mean (Standard Deviation)
Unit of Measure: Percentage change in HRQL score
month 3 (n=67,66) 20.7  (60.26) 40.1  (135.47)
month 6 (n= 55,56) 19.6  (47.78) 52.2  (169.47)
month 12 (n=20,20) 54.9  (95.83) 111.5  (266.75)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pasireotide 600 ug Pasireotide 900 ug
Hide Arm/Group Description At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country. At randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was <= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotode was available commercially in their country.
All-Cause Mortality
Pasireotide 600 ug Pasireotide 900 ug
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pasireotide 600 ug Pasireotide 900 ug
Affected / at Risk (%) Affected / at Risk (%)
Total   23/82 (28.05%)   25/80 (31.25%) 
Cardiac disorders     
Atrioventricular block second degree  1  0/82 (0.00%)  1/80 (1.25%) 
Ear and labyrinth disorders     
Ear haemorrhage  1  1/82 (1.22%)  0/80 (0.00%) 
Tympanic membrane perforation  1  1/82 (1.22%)  0/80 (0.00%) 
Vertigo positional  1  0/82 (0.00%)  1/80 (1.25%) 
Endocrine disorders     
Adrenal insufficiency  1  0/82 (0.00%)  2/80 (2.50%) 
Pituitary-dependent Cushing's syndrome  1  3/82 (3.66%)  3/80 (3.75%) 
Gastrointestinal disorders     
Abdominal pain  1  0/82 (0.00%)  1/80 (1.25%) 
Anal fistula  1  1/82 (1.22%)  0/80 (0.00%) 
Constipation  1  0/82 (0.00%)  1/80 (1.25%) 
Diarrhoea  1  2/82 (2.44%)  0/80 (0.00%) 
Diverticular perforation  1  1/82 (1.22%)  0/80 (0.00%) 
Inguinal hernia  1  0/82 (0.00%)  1/80 (1.25%) 
Pancreatitis  1  1/82 (1.22%)  0/80 (0.00%) 
Tongue movement disturbance  1  0/82 (0.00%)  1/80 (1.25%) 
Umbilical hernia  1  0/82 (0.00%)  1/80 (1.25%) 
General disorders     
Disease progression  1  1/82 (1.22%)  1/80 (1.25%) 
Drug ineffective  1  1/82 (1.22%)  1/80 (1.25%) 
Microlithiasis  1  0/82 (0.00%)  1/80 (1.25%) 
Hepatobiliary disorders     
Bile duct stone  1  0/82 (0.00%)  1/80 (1.25%) 
Cholangitis  1  1/82 (1.22%)  0/80 (0.00%) 
Cholecystitis  1  0/82 (0.00%)  1/80 (1.25%) 
Cholecystitis acute  1  2/82 (2.44%)  0/80 (0.00%) 
Cholelithiasis  1  4/82 (4.88%)  2/80 (2.50%) 
Infections and infestations     
Abscess intestinal  1  1/82 (1.22%)  0/80 (0.00%) 
Cellulitis  1  0/82 (0.00%)  1/80 (1.25%) 
Cervicitis  1  0/82 (0.00%)  1/80 (1.25%) 
Diverticulitis  1  1/82 (1.22%)  0/80 (0.00%) 
Escherichia urinary tract infection  1  1/82 (1.22%)  0/80 (0.00%) 
Nail infection  1  1/82 (1.22%)  0/80 (0.00%) 
Pneumonia  1  1/82 (1.22%)  0/80 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  0/82 (0.00%)  1/80 (1.25%) 
Toxicity to various agents  1  1/82 (1.22%)  0/80 (0.00%) 
Investigations     
Electrocardiogram QT prolonged  1  0/82 (0.00%)  1/80 (1.25%) 
Lipase increased  1  1/82 (1.22%)  0/80 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/82 (1.22%)  3/80 (3.75%) 
Food intolerance  1  0/82 (0.00%)  1/80 (1.25%) 
Hyperglycaemia  1  1/82 (1.22%)  4/80 (5.00%) 
Hypoglycaemia  1  1/82 (1.22%)  0/80 (0.00%) 
Type 2 diabetes mellitus  1  1/82 (1.22%)  0/80 (0.00%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  0/82 (0.00%)  1/80 (1.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Pituitary tumour benign  1  1/82 (1.22%)  2/80 (2.50%) 
Secretory adenoma of pituitary  1  0/82 (0.00%)  1/80 (1.25%) 
Nervous system disorders     
Cerebrovascular accident  1  0/82 (0.00%)  1/80 (1.25%) 
Cranial nerve paralysis  1  0/82 (0.00%)  1/80 (1.25%) 
Dizziness  1  0/82 (0.00%)  1/80 (1.25%) 
Dysarthria  1  0/82 (0.00%)  1/80 (1.25%) 
Intracranial aneurysm  1  0/82 (0.00%)  1/80 (1.25%) 
Somnolence  1  0/82 (0.00%)  1/80 (1.25%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  1/82 (1.22%)  0/80 (0.00%) 
Psychiatric disorders     
Agitation  1  0/82 (0.00%)  1/80 (1.25%) 
Reproductive system and breast disorders     
Adenomyosis  1  0/82 (0.00%)  1/80 (1.25%) 
Uterine polyp  1  1/82 (1.22%)  1/80 (1.25%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  1/82 (1.22%)  0/80 (0.00%) 
Oropharyngeal pain  1  1/82 (1.22%)  0/80 (0.00%) 
Vascular disorders     
Hypertensive crisis  1  0/82 (0.00%)  1/80 (1.25%) 
Hypertensive emergency  1  0/82 (0.00%)  1/80 (1.25%) 
Hypotension  1  1/82 (1.22%)  1/80 (1.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pasireotide 600 ug Pasireotide 900 ug
Affected / at Risk (%) Affected / at Risk (%)
Total   78/82 (95.12%)   79/80 (98.75%) 
Blood and lymphatic system disorders     
Anaemia  1  1/82 (1.22%)  5/80 (6.25%) 
Iron deficiency anaemia  1  3/82 (3.66%)  4/80 (5.00%) 
Cardiac disorders     
Sinus bradycardia  1  8/82 (9.76%)  2/80 (2.50%) 
Ear and labyrinth disorders     
Vertigo  1  4/82 (4.88%)  6/80 (7.50%) 
Endocrine disorders     
Hypothyroidism  1  3/82 (3.66%)  4/80 (5.00%) 
Eye disorders     
Vision blurred  1  3/82 (3.66%)  4/80 (5.00%) 
Gastrointestinal disorders     
Abdominal distension  1  6/82 (7.32%)  6/80 (7.50%) 
Abdominal pain  1  19/82 (23.17%)  21/80 (26.25%) 
Abdominal pain upper  1  11/82 (13.41%)  8/80 (10.00%) 
Constipation  1  9/82 (10.98%)  4/80 (5.00%) 
Diarrhoea  1  49/82 (59.76%)  46/80 (57.50%) 
Dyspepsia  1  1/82 (1.22%)  5/80 (6.25%) 
Faeces soft  1  3/82 (3.66%)  4/80 (5.00%) 
Haemorrhoids  1  3/82 (3.66%)  4/80 (5.00%) 
Nausea  1  40/82 (48.78%)  47/80 (58.75%) 
Vomiting  1  3/82 (3.66%)  9/80 (11.25%) 
General disorders     
Asthenia  1  13/82 (15.85%)  6/80 (7.50%) 
Fatigue  1  12/82 (14.63%)  24/80 (30.00%) 
Injection site haemorrhage  1  1/82 (1.22%)  4/80 (5.00%) 
Injection site pain  1  3/82 (3.66%)  4/80 (5.00%) 
Malaise  1  2/82 (2.44%)  5/80 (6.25%) 
Oedema peripheral  1  9/82 (10.98%)  6/80 (7.50%) 
Hepatobiliary disorders     
Cholelithiasis  1  25/82 (30.49%)  25/80 (31.25%) 
Infections and infestations     
Gastroenteritis  1  0/82 (0.00%)  4/80 (5.00%) 
Influenza  1  10/82 (12.20%)  5/80 (6.25%) 
Nasopharyngitis  1  12/82 (14.63%)  12/80 (15.00%) 
Upper respiratory tract infection  1  6/82 (7.32%)  2/80 (2.50%) 
Urinary tract infection  1  4/82 (4.88%)  6/80 (7.50%) 
Injury, poisoning and procedural complications     
Contusion  1  0/82 (0.00%)  4/80 (5.00%) 
Procedural pain  1  1/82 (1.22%)  4/80 (5.00%) 
Investigations     
Alanine aminotransferase increased  1  12/82 (14.63%)  6/80 (7.50%) 
Aspartate aminotransferase increased  1  6/82 (7.32%)  3/80 (3.75%) 
Blood alkaline phosphatase increased  1  6/82 (7.32%)  1/80 (1.25%) 
Blood glucose increased  1  6/82 (7.32%)  3/80 (3.75%) 
Blood insulin decreased  1  1/82 (1.22%)  4/80 (5.00%) 
Electrocardiogram QT prolonged  1  5/82 (6.10%)  7/80 (8.75%) 
Gamma-glutamyltransferase increased  1  11/82 (13.41%)  7/80 (8.75%) 
Glycosylated haemoglobin increased  1  10/82 (12.20%)  8/80 (10.00%) 
International normalised ratio increased  1  1/82 (1.22%)  4/80 (5.00%) 
Lipase increased  1  7/82 (8.54%)  5/80 (6.25%) 
Low density lipoprotein increased  1  5/82 (6.10%)  3/80 (3.75%) 
Prothrombin time prolonged  1  2/82 (2.44%)  4/80 (5.00%) 
Weight decreased  1  3/82 (3.66%)  5/80 (6.25%) 
Metabolism and nutrition disorders     
Decreased appetite  1  8/82 (9.76%)  9/80 (11.25%) 
Diabetes mellitus  1  17/82 (20.73%)  18/80 (22.50%) 
Hypercholesterolaemia  1  8/82 (9.76%)  12/80 (15.00%) 
Hyperglycaemia  1  31/82 (37.80%)  35/80 (43.75%) 
Hyperlipidaemia  1  5/82 (6.10%)  3/80 (3.75%) 
Hypertriglyceridaemia  1  6/82 (7.32%)  5/80 (6.25%) 
Hypoglycaemia  1  12/82 (14.63%)  5/80 (6.25%) 
Hypokalaemia  1  6/82 (7.32%)  6/80 (7.50%) 
Type 2 diabetes mellitus  1  10/82 (12.20%)  5/80 (6.25%) 
Vitamin B12 deficiency  1  2/82 (2.44%)  5/80 (6.25%) 
Vitamin D deficiency  1  5/82 (6.10%)  5/80 (6.25%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/82 (7.32%)  10/80 (12.50%) 
Back pain  1  5/82 (6.10%)  7/80 (8.75%) 
Muscle spasms  1  1/82 (1.22%)  4/80 (5.00%) 
Myalgia  1  11/82 (13.41%)  6/80 (7.50%) 
Neck pain  1  0/82 (0.00%)  4/80 (5.00%) 
Pain in extremity  1  7/82 (8.54%)  4/80 (5.00%) 
Nervous system disorders     
Dizziness  1  9/82 (10.98%)  9/80 (11.25%) 
Dysgeusia  1  3/82 (3.66%)  4/80 (5.00%) 
Headache  1  25/82 (30.49%)  25/80 (31.25%) 
Migraine  1  0/82 (0.00%)  4/80 (5.00%) 
Somnolence  1  2/82 (2.44%)  4/80 (5.00%) 
Psychiatric disorders     
Anxiety  1  6/82 (7.32%)  10/80 (12.50%) 
Depression  1  3/82 (3.66%)  4/80 (5.00%) 
Insomnia  1  3/82 (3.66%)  13/80 (16.25%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  5/82 (6.10%)  3/80 (3.75%) 
Oropharyngeal pain  1  1/82 (1.22%)  4/80 (5.00%) 
Skin and subcutaneous tissue disorders     
Acne  1  5/82 (6.10%)  2/80 (2.50%) 
Alopecia  1  10/82 (12.20%)  11/80 (13.75%) 
Dry skin  1  5/82 (6.10%)  5/80 (6.25%) 
Ecchymosis  1  1/82 (1.22%)  4/80 (5.00%) 
Pruritus  1  6/82 (7.32%)  7/80 (8.75%) 
Rash  1  6/82 (7.32%)  4/80 (5.00%) 
Skin exfoliation  1  5/82 (6.10%)  3/80 (3.75%) 
Vascular disorders     
Hypertension  1  10/82 (12.20%)  8/80 (10.00%) 
Hypotension  1  4/82 (4.88%)  5/80 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 17.0
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.

Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

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

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00434148     History of Changes
Other Study ID Numbers: CSOM230B2305
2006-004111-22 ( EudraCT Number )
First Submitted: February 9, 2007
First Posted: February 12, 2007
Results First Submitted: January 3, 2013
Results First Posted: February 6, 2013
Last Update Posted: March 8, 2016