Cushing's Disease
Conditions
Keywords
Cushing's Disease, pasireotide, SOM230
Brief summary
This study will evaluate the safety and efficacy of two different doses of Pasireotide in patients with de novo or recurrent/persistent Cushing's Disease.
Interventions
DRUGPasireotide
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or greater * Confirmed diagnosis of ACTH-dependent Cushing's disease * Not considered candidate for pituitary surgery
Exclusion criteria
* History of pituitary irradiation in the last 10 years * Cushing's syndrome not caused by pituitary tumor * Patients with active malignant disease (cancer) in the last 5 years * Women who are pregnant or lactating Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First UFC Response | 12 months | Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response. |
| Percent Change From Baseline in Serum Cortisol | 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 | Blood samlpes were drawn to obtain serum cortisol levels. A negative change from baseline indicates improvement. |
| Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | 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 | Blood samples were drawn to obtain ACTH levels. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | Sitting blood pressure assessments were performed at every study visit. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | baseline, month 3, month 6, month 12, month 24, month 36, month 48 and month 60 | BMI was determined by using height and weight measurements. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | Waist circumference was measured with a measuring tape correctly positioned. A negative change from baseline indicates improvement. |
| Change From Baseline in mUFC | baseline, 3 months, 12 months | Twenty four hour urine samples were collected to obtain mUFC measurements. A negative change from baseline indicates improvement. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | baseline, month 3, month 6, month 12, month 18, month 24 | 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. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | 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. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | 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. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | Body composition as in percentage of body fat by region was assessed by total body scan. A negative change from baseline indicates improvement. |
| Change From Baseline in Tumor Volume | baseline, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78 months | Pituitary magnetic resonance imaging (MRI) was performed to determine tumor volume. A negative change from baseline indicates imrpovement. |
| Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | baseline, 3 months, 6 months, 12 months | 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. |
| Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | baseline, month 3, month 6, month 12, month 24, month 36, month 48, month 60 | Blood samples were drawn to obtain total cholesterol and triglycerides' levels. A negative change from baseline indicates improvement. |
Countries
Argentina, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Israel, Italy, Mexico, Poland, Portugal, Spain, Turkey (Türkiye), United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide 600 ug 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. | 82 |
| Pasireotide 900 ug 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. | 80 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure result | 0 | 1 |
| Overall Study | Administrative problems | 6 | 10 |
| Overall Study | Adverse Event | 18 | 18 |
| Overall Study | Condition no longer requires study drug | 1 | 0 |
| Overall Study | Lack of Efficacy | 25 | 28 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 4 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 15 |
Baseline characteristics
| Characteristic | Pasireotide 600 ug | Pasireotide 900 ug | Total |
|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 12.97 | 39.9 years STANDARD_DEVIATION 10.77 | 40.2 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 62 Participants | 64 Participants | 126 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 78 / 82 | 79 / 80 |
| serious Total, serious adverse events | 23 / 82 | 25 / 80 |
Outcome results
Primary
Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Pasireotide 600 ug | Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group | 12 Responders |
| Pasireotide 900 ug | Number of mUFC (Urinary Free Cortisol) Responders by Randomized Dose Group | 21 Responders |
Secondary
Change From Baseline in mUFC
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Change From Baseline in mUFC | month 3 (n=61,62) | -375.8 nmol/24h | Standard Deviation 631.07 |
| Pasireotide 600 ug | Change From Baseline in mUFC | month 12 (n=37,35) | -572.6 nmol/24h | Standard Deviation 941.44 |
| Pasireotide 900 ug | Change From Baseline in mUFC | month 3 (n=61,62) | -343.4 nmol/24h | Standard Deviation 485.48 |
| Pasireotide 900 ug | Change From Baseline in mUFC | month 12 (n=37,35) | -350.7 nmol/24h | Standard Deviation 380.25 |
Secondary
Change From Baseline in Tumor Volume
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 78 (n=1, 0) | 77.2 cm^3 | — |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 6 (n=25, 28) | 9.3 cm^3 | Standard Deviation 44.02 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 12 (n=15, 18) | -8.1 cm^3 | Standard Deviation 62.17 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 18 (n=8, 11) | -18.1 cm^3 | Standard Deviation 71.62 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 24 (n=7, 13) | -27.4 cm^3 | Standard Deviation 82.68 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 30 (n=6, 8) | -52.1 cm^3 | Standard Deviation 55.2 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 36 (n=3, 5) | -94.1 cm^3 | Standard Deviation 10.15 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 42 (n=3, 3) | -95.2 cm^3 | Standard Deviation 8.4 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 48 (n=3, 3) | -20.5 cm^3 | Standard Deviation 130.9 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 54 (n=3, 2) | -29.1 cm^3 | Standard Deviation 107.4 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 60 (n=3, 2) | -13.5 cm^3 | Standard Deviation 136.97 |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 66 (n= 1, 1) | -100.0 cm^3 | — |
| Pasireotide 600 ug | Change From Baseline in Tumor Volume | month 72 (n=1, 0) | 45.6 cm^3 | — |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 60 (n=3, 2) | 127.6 cm^3 | Standard Deviation 321.88 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 42 (n=3, 3) | 84.0 cm^3 | Standard Deviation 282.6 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 6 (n=25, 28) | -19.0 cm^3 | Standard Deviation 36.82 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 72 (n=1, 0) | NA cm^3 | — |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 12 (n=15, 18) | -43.8 cm^3 | Standard Deviation 49.47 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 48 (n=3, 3) | 29.2 cm^3 | Standard Deviation 164.67 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 18 (n=8, 11) | -36.0 cm^3 | Standard Deviation 65.42 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 66 (n= 1, 1) | 269.8 cm^3 | — |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 24 (n=7, 13) | -11.5 cm^3 | Standard Deviation 66.28 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 54 (n=3, 2) | 20.3 cm^3 | Standard Deviation 170.15 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 30 (n=6, 8) | -20.9 cm^3 | Standard Deviation 77.16 |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 78 (n=1, 0) | NA cm^3 | — |
| Pasireotide 900 ug | Change From Baseline in Tumor Volume | month 36 (n=3, 5) | -27.6 cm^3 | Standard Deviation 78.86 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 6 (n=56,55) | -4.6 score on a scale | Standard Deviation 9.49 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 18 (n=6,6) | -1.3 score on a scale | Standard Deviation 5.24 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 12 (n=38,37) | -4.6 score on a scale | Standard Deviation 9.19 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 24 (n=0,1) | NA score on a scale | — |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 3 (n=66,65) | -4.6 score on a scale | Standard Deviation 8.29 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 24 (n=0,1) | -12.0 score on a scale | — |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 3 (n=66,65) | -1.9 score on a scale | Standard Deviation 9.88 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 6 (n=56,55) | -5.5 score on a scale | Standard Deviation 8.81 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 12 (n=38,37) | -5.2 score on a scale | Standard Deviation 9.94 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Beck Depression Inventory (BDI-II) Score | month 18 (n=6,6) | -7.8 score on a scale | Standard Deviation 5.78 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 12 (n=29,22) | -3.0 Percentage of body fat | Standard Deviation 4.23 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 36 (n=5,8) | -2.0 Percentage of body fat | Standard Deviation 4.2 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 6 (n=39,32) | -0.4 Percentage of body fat | Standard Deviation 3.77 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 48 (n=4,7) | -2.0 Percentage of body fat | Standard Deviation 5.07 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 24 (n=13,14) | -1.9 Percentage of body fat | Standard Deviation 3.24 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 60 (n=4,6) | -2.8 Percentage of body fat | Standard Deviation 4.64 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 3 (n=2,2) | 2.9 Percentage of body fat | Standard Deviation 1.48 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 60 (n=4,6) | -0.5 Percentage of body fat | Standard Deviation 4.97 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 3 (n=2,2) | 0.3 Percentage of body fat | Standard Deviation 0.78 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 6 (n=39,32) | -0.9 Percentage of body fat | Standard Deviation 4.06 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 12 (n=29,22) | -1.6 Percentage of body fat | Standard Deviation 4.27 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 24 (n=13,14) | -1.9 Percentage of body fat | Standard Deviation 5.7 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 36 (n=5,8) | -1.1 Percentage of body fat | Standard Deviation 4.94 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Composition | Month 48 (n=4,7) | 0.1 Percentage of body fat | Standard Deviation 5.63 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 60 (n=8,8) | -2.8 kg/m^2 | Standard Deviation 1.85 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 3 (n=70,67) | -1.0 kg/m^2 | Standard Deviation 1.26 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 6 (n=59,57) | -1.2 kg/m^2 | Standard Deviation 1.64 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 12 (n=40,39) | -2.1 kg/m^2 | Standard Deviation 2.19 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 24 (n=18,23) | -3.4 kg/m^2 | Standard Deviation 2.97 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 36 (n=10,13) | -2.9 kg/m^2 | Standard Deviation 2.47 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 48 (n=9,10) | -3.1 kg/m^2 | Standard Deviation 2.14 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 60 (n=8,8) | -2.0 kg/m^2 | Standard Deviation 2.2 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 24 (n=18,23) | -3.0 kg/m^2 | Standard Deviation 2.67 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 3 (n=70,67) | -1.4 kg/m^2 | Standard Deviation 1.29 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 48 (n=9,10) | -2.4 kg/m^2 | Standard Deviation 2.6 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 6 (n=59,57) | -2.1 kg/m^2 | Standard Deviation 1.72 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 36 (n=10,13) | -3.3 kg/m^2 | Standard Deviation 3.48 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Body Mass Index (BMI) | month 12 (n=40,39) | -2.8 kg/m^2 | Standard Deviation 2.21 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 3 (n=2,2) | 0 mg/cm^3 | Standard Deviation 0.02 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 6 (n=47,39) | 0 mg/cm^3 | Standard Deviation 0.06 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 12 (n=33,29) | 0 mg/cm^3 | Standard Deviation 0.07 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 24 (n=16,16) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 36 (n=8,9) | 0 mg/cm^3 | Standard Deviation 0.09 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 48 (n=9,8) | 0 mg/cm^3 | Standard Deviation 0.12 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 60 (n=7,6) | 0 mg/cm^3 | Standard Deviation 0.14 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 3 (2,2) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 6 (n=46,38) | 0 mg/cm^3 | Standard Deviation 0.07 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 12 (n=33,26) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 24 (n=16,13) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 36 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.03 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 48 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 60 (n=7,6) | -0.1 mg/cm^3 | Standard Deviation 0.14 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 3 (n=2,2) | 0 mg/cm^3 | Standard Deviation 0 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 6 (n=46,38) | 0 mg/cm^3 | Standard Deviation 0.03 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 12 (n=33,28) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 24 (n=16,14) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 36 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.02 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 48 (n=9,7) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 60 (7,6) | 0 mg/cm^3 | Standard Deviation 0.1 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 24 (n=16,13) | 0 mg/cm^3 | Standard Deviation 0.03 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 3 (n=2,2) | 0 mg/cm^3 | Standard Deviation 0 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 36 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 6 (n=47,39) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 36 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.06 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 12 (n=33,29) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 12 (n=33,28) | 0 mg/cm^3 | Standard Deviation 0.07 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 24 (n=16,16) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 48 (n=8,8) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 36 (n=8,9) | 0.1 mg/cm^3 | Standard Deviation 0.12 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 60 (7,6) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 48 (n=9,8) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 60 (n=7,6) | 0 mg/cm^3 | Standard Deviation 0.06 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Lumbar vertebrae, month 60 (n=7,6) | 0 mg/cm^3 | Standard Deviation 0.08 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 24 (n=16,14) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 3 (2,2) | 0 mg/cm^3 | Standard Deviation 0.01 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 3 (n=2,2) | 0 mg/cm^3 | Standard Deviation 0.03 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 6 (n=46,38) | 0 mg/cm^3 | Standard Deviation 0.05 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 48 (n=9,7) | 0 mg/cm^3 | Standard Deviation 0.04 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (total hip), month 12 (n=33,26) | 0 mg/cm^3 | Standard Deviation 0.03 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Bone Mineral Density (BMD) | Proximal femur (femur neck), month 6 (n=46,38) | 0 mg/cm^3 | Standard Deviation 0.05 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 12 (n=30,35) | -1.3 score on a scale | Standard Deviation 1.99 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 36 (n=7,12) | -3.7 score on a scale | Standard Deviation 2.69 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 6 (n=44,47) | -0.9 score on a scale | Standard Deviation 2.88 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 48 (n=6,10) | -6.0 score on a scale | Standard Deviation 3.85 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 24 (n=12,22) | -2.8 score on a scale | Standard Deviation 2.72 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 60 (n=5,8) | -5.0 score on a scale | Standard Deviation 3.32 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 3 (n=52,50) | -1.3 score on a scale | Standard Deviation 3.02 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 60 (n=5,8) | -2.9 score on a scale | Standard Deviation 3.23 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 3 (n=52,50) | -1.3 score on a scale | Standard Deviation 3.46 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 6 (n=44,47) | -2.4 score on a scale | Standard Deviation 4.7 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 12 (n=30,35) | -3.5 score on a scale | Standard Deviation 4.65 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 24 (n=12,22) | -4.0 score on a scale | Standard Deviation 4.34 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 36 (n=7,12) | -3.2 score on a scale | Standard Deviation 4.09 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Ferriman-Galway Hirsutism Score | month 48 (n=6,10) | -2.5 score on a scale | Standard Deviation 2.84 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 6 (n=59,57) | -6.8 mmHg | Standard Deviation 19.35 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 3 (n=70,67) | -7.4 mmHg | Standard Deviation 17.37 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 12 (n=39,39) | -2.8 mmHg | Standard Deviation 18.4 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 24 (n=18,23) | -11.6 mmHg | Standard Deviation 12.82 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 36 (n=10,13) | -3.0 mmHg | Standard Deviation 17.08 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 48 (n=9,10) | -12.0 mmHg | Standard Deviation 14.15 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 60 (n=7,8) | -12.8 mmHg | Standard Deviation 17.1 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 3 (n=70,67) | -3.3 mmHg | Standard Deviation 11.01 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP , month 6 (n=59,57) | -4.2 mmHg | Standard Deviation 13.54 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 12 (n=39,39) | -2.0 mmHg | Standard Deviation 11.65 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 24 (n=18,23) | -8.1 mmHg | Standard Deviation 11.35 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 36 (n=10,13) | -6.8 mmHg | Standard Deviation 14.17 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 48 (n=9,10) | -11.7 mmHg | Standard Deviation 12.02 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 60 (n=7,8) | -9.1 mmHg | Standard Deviation 9.79 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 24 (n=18,23) | -6.4 mmHg | Standard Deviation 9.37 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 6 (n=59,57) | -11.4 mmHg | Standard Deviation 15.92 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 24 (n=18,23) | -11.0 mmHg | Standard Deviation 11.58 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 60 (n=7,8) | -2.0 mmHg | Standard Deviation 11.83 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 3 (n=70,67) | -4.1 mmHg | Standard Deviation 13.11 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 3 (n=70,67) | -9.9 mmHg | Standard Deviation 17.01 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 48 (n=9,10) | -1.0 mmHg | Standard Deviation 9.3 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 12 (n=39,39) | -9.4 mmHg | Standard Deviation 14.61 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP , month 6 (n=59,57) | -5.0 mmHg | Standard Deviation 11.56 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 36 (n=10,13) | -7.3 mmHg | Standard Deviation 8.25 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 36 (n=10,13) | -11.5 mmHg | Standard Deviation 16.23 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 12 (n=39,39) | -5.4 mmHg | Standard Deviation 10.86 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting SBP, month 48 (n=9,10) | -3.6 mmHg | Standard Deviation 14.56 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Sitting Sytolic Blood Pressure (SBP) and Sitting Diastolic Blood Pressure (DBP) | Sitting DBP, month 60 (n=7,8) | 0.7 mmHg | Standard Deviation 7.34 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 60 (n=8,8) | -1.5 mmol/L | Standard Deviation 1.57 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 12 (n=40,39) | -0.5 mmol/L | Standard Deviation 1.29 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 6 (n=59,55) | 0 mmol/L | Standard Deviation 0.92 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 6 (n=59,55) | -0.4 mmol/L | Standard Deviation 1.24 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 12 (n=40,39) | -0.1 mmol/L | Standard Deviation 0.77 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 36 (n=10,12) | -0.8 mmol/L | Standard Deviation 1.24 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 24 (n=18,22) | 0 mmol/L | Standard Deviation 1.05 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 24 (n=18,22) | -0.6 mmol/L | Standard Deviation 1.39 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 36 (n=10,12) | -0.2 mmol/L | Standard Deviation 0.99 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 3 (n=70,67) | 0.1 mmol/L | Standard Deviation 1.07 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 48 (n=9,10) | -0.5 mmol/L | Standard Deviation 0.94 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 48 (n=9,10) | -0.9 mmol/L | Standard Deviation 1.63 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 60 (n=8,8) | -0.7 mmol/L | Standard Deviation 1.01 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 3 (n=70,67) | -0.2 mmol/L | Standard Deviation 1.06 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 60 (n=8,8) | 0.2 mmol/L | Standard Deviation 1.02 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 36 (n=10,12) | -0.1 mmol/L | Standard Deviation 0.64 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 60 (n=8,8) | -0.4 mmol/L | Standard Deviation 1 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 3 (n=70,67) | -0.3 mmol/L | Standard Deviation 1.01 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 12 (n=40,39) | -0.6 mmol/L | Standard Deviation 1.18 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 24 (n=18,22) | -0.3 mmol/L | Standard Deviation 0.81 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 48 (n=9,10) | -0.4 mmol/L | Standard Deviation 0.8 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 3 (n=70,67) | 0.1 mmol/L | Standard Deviation 1.01 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 6 (n=59,55) | 0.1 mmol/L | Standard Deviation 1 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 12 (n=40,39) | -0.2 mmol/L | Standard Deviation 0.69 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 24 (n=18,22) | 0 mmol/L | Standard Deviation 0.82 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 36 (n=10,12) | 0.3 mmol/L | Standard Deviation 1.38 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Triglycerides, month 48 (n=9,10) | 0.4 mmol/L | Standard Deviation 1.32 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Total Cholesterol and Triglycerides | Cholesterol, month 6 (n=59,55) | -0.4 mmol/L | Standard Deviation 0.98 |
Secondary
Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 12(n=34,35) | -4.4 cm | Standard Deviation 9.4 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 36 (n=9,13) | -7.8 cm | Standard Deviation 10.46 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 6 (n=53,54) | -1.9 cm | Standard Deviation 8.33 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 48 (n=8,10) | -8.3 cm | Standard Deviation 11.59 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 24 ( n=17,22) | -8.7 cm | Standard Deviation 9.54 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 60 (n=7,8) | -7.3 cm | Standard Deviation 12.08 |
| Pasireotide 600 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 3 (n=64,66) | -1.0 cm | Standard Deviation 10.47 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 60 (n=7,8) | -4.6 cm | Standard Deviation 10.9 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 3 (n=64,66) | -2.2 cm | Standard Deviation 5.23 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 6 (n=53,54) | -3.4 cm | Standard Deviation 5.39 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 12(n=34,35) | -5.6 cm | Standard Deviation 7.86 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 24 ( n=17,22) | -5.1 cm | Standard Deviation 10.22 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 36 (n=9,13) | -6.4 cm | Standard Deviation 9.97 |
| Pasireotide 900 ug | Mean Change From Baseline in Clinical Signs and Symptoms of Cushing's Disease: Waist Circumference | month 48 (n=8,10) | -5.1 cm | Standard Deviation 10.03 |
Secondary
Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 3 (n=67,66) | 20.7 Percentage change in HRQL score | Standard Deviation 60.26 |
| Pasireotide 600 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 6 (n= 55,56) | 19.6 Percentage change in HRQL score | Standard Deviation 47.78 |
| Pasireotide 600 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 12 (n=20,20) | 54.9 Percentage change in HRQL score | Standard Deviation 95.83 |
| Pasireotide 900 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 3 (n=67,66) | 40.1 Percentage change in HRQL score | Standard Deviation 135.47 |
| Pasireotide 900 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 6 (n= 55,56) | 52.2 Percentage change in HRQL score | Standard Deviation 169.47 |
| Pasireotide 900 ug | Percentage Change From Baseline in Health Related Quality of Life (HRQL) Score | month 12 (n=20,20) | 111.5 Percentage change in HRQL score | Standard Deviation 266.75 |
Secondary
Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 4 (n=66,61) | -7.2 percent change | Standard Deviation 38.42 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 21 (n=20,23) | -1.5 percent change | Standard Deviation 51.52 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 15 (n=26,26) | -14.5 percent change | Standard Deviation 43.44 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 24 (n=18,21) | -10.9 percent change | Standard Deviation 47.95 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 5 (n=62,55) | -3.0 percent change | Standard Deviation 42.5 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 27 (n=16,18) | -10.4 percent change | Standard Deviation 53.33 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 1.5 (n=74,69) | -13.4 percent change | Standard Deviation 31.64 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 30 (n=14,18) | -14.7 percent change | Standard Deviation 56.17 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 6 (n=58,55) | -8.4 percent change | Standard Deviation 43.61 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 36 (n=10,13) | 19.1 percent change | Standard Deviation 112.26 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 33 (n=13,14) | -9.4 percent change | Standard Deviation 55.01 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 39 (n=10,12) | -20.9 percent change | Standard Deviation 48.68 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 7 (n=52,52) | -11.4 percent change | Standard Deviation 45.25 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 42 (n=10,12) | -6.7 percent change | Standard Deviation 59.61 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 2 (n=72,66) | -7.7 percent change | Standard Deviation 40.86 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 45 (n=9,11) | 11.9 percent change | Standard Deviation 89.59 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 8 (n=48,46) | -5.0 percent change | Standard Deviation 51.75 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 48 (n=9,9) | -10.8 percent change | Standard Deviation 65.52 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 57 (n=7,7) | 9.6 percent change | Standard Deviation 59.86 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 51 (n=9,9) | 0.0 percent change | Standard Deviation 65.82 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 9 (n=46,47) | -5.3 percent change | Standard Deviation 55.27 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 54 (n=9,9) | 4.6 percent change | Standard Deviation 77.49 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 2.5 (n=69,65) | -8.2 percent change | Standard Deviation 37.32 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 60 (n=8,8) | 9.6 percent change | Standard Deviation 61.38 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 10 (n=42,46) | -10.2 percent change | Standard Deviation 48.82 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 63 (n=6,7) | 11.9 percent change | Standard Deviation 73.78 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 0.5 (n=78,75) | 9.3 percent change | Standard Deviation 181.17 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 66 (n=4,6) | 25.3 percent change | Standard Deviation 75.31 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 11 (n=42,40) | -11.5 percent change | Standard Deviation 44.52 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 69 (n=3,5) | 38.9 percent change | Standard Deviation 78.34 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 3 (n=69,66) | -9.2 percent change | Standard Deviation 40.85 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 72 (n=3,3) | 35.6 percent change | Standard Deviation 78.48 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 12 (n=39,39) | -7.4 percent change | Standard Deviation 53.83 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 75 (n=2,3) | -5.0 percent change | Standard Deviation 77.78 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 1 (n=78,71) | -10.0 percent change | Standard Deviation 37.29 |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 78 (n=1,1) | 50.0 percent change | — |
| Pasireotide 600 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 18 (n=26,25) | -5.9 percent change | Standard Deviation 57.56 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 78 (n=1,1) | -11.1 percent change | — |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 0.5 (n=78,75) | -15.9 percent change | Standard Deviation 30.75 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 12 (n=39,39) | -26.5 percent change | Standard Deviation 33.38 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 57 (n=7,7) | -5.0 percent change | Standard Deviation 45.19 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 1 (n=78,71) | -19.1 percent change | Standard Deviation 30.47 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 1.5 (n=74,69) | -10.5 percent change | Standard Deviation 38.05 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 2 (n=72,66) | -13.2 percent change | Standard Deviation 35.38 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 2.5 (n=69,65) | -12.0 percent change | Standard Deviation 47.02 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 3 (n=69,66) | -16.3 percent change | Standard Deviation 31.93 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 4 (n=66,61) | -12.8 percent change | Standard Deviation 44.06 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 5 (n=62,55) | -15.0 percent change | Standard Deviation 38.89 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 6 (n=58,55) | -17.3 percent change | Standard Deviation 35.6 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 7 (n=52,52) | -14.6 percent change | Standard Deviation 30.88 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 8 (n=48,46) | -17.0 percent change | Standard Deviation 36.87 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 9 (n=46,47) | -18.2 percent change | Standard Deviation 35.87 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 10 (n=42,46) | -18.2 percent change | Standard Deviation 34.18 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 11 (n=42,40) | -17.4 percent change | Standard Deviation 39.06 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 15 (n=26,26) | -16.3 percent change | Standard Deviation 32.01 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 18 (n=26,25) | -21.2 percent change | Standard Deviation 32.91 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 21 (n=20,23) | -17.3 percent change | Standard Deviation 34.34 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 24 (n=18,21) | -18.0 percent change | Standard Deviation 26.53 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 27 (n=16,18) | -12.5 percent change | Standard Deviation 39.39 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 33 (n=13,14) | -2.4 percent change | Standard Deviation 33.07 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 36 (n=10,13) | 1.2 percent change | Standard Deviation 35.33 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 39 (n=10,12) | -5.3 percent change | Standard Deviation 40.02 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 42 (n=10,12) | 2.7 percent change | Standard Deviation 42.35 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 45 (n=9,11) | 8.1 percent change | Standard Deviation 50.09 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 48 (n=9,9) | 11.7 percent change | Standard Deviation 55.85 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 51 (n=9,9) | -3.1 percent change | Standard Deviation 48.21 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 54 (n=9,9) | 7.3 percent change | Standard Deviation 52.94 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 60 (n=8,8) | -1.3 percent change | Standard Deviation 39.01 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 63 (n=6,7) | 15.4 percent change | Standard Deviation 50.66 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 66 (n=4,6) | 18.3 percent change | Standard Deviation 61.35 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 69 (n=3,5) | -1.2 percent change | Standard Deviation 23.98 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 72 (n=3,3) | 22.0 percent change | Standard Deviation 46.15 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 75 (n=2,3) | 23.1 percent change | Standard Deviation 110.92 |
| Pasireotide 900 ug | Percent Change From Baseline in Mean Adrenocorticotropic Hormone (ACTH) | month 30 (n=14,18) | -20.0 percent change | Standard Deviation 40.82 |
Secondary
Percent Change From Baseline in Serum Cortisol
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 11 (n=41,41) | -8.2 Percent change | Standard Deviation 38.19 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 42 (n=10,12) | -17.8 Percent change | Standard Deviation 39.54 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 10 (n=42,47) | -11.2 Percent change | Standard Deviation 30.25 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 45 (n=10,11) | -12.5 Percent change | Standard Deviation 44.89 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 12 (n=39,38) | -11.6 Percent change | Standard Deviation 33.75 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 48 (n=9,11) | -19.7 Percent change | Standard Deviation 37.88 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 66 (n=4,6) | -6.7 Percent change | Standard Deviation 29.29 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 51 (n=9,9) | -17.6 Percent change | Standard Deviation 34.6 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 15 (n=26,26) | -10.5 Percent change | Standard Deviation 30.14 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 54 (n=9,9) | -25.0 Percent change | Standard Deviation 30.49 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 30 (n=14,19) | -22.8 Percent change | Standard Deviation 35.43 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 57 (n=8,8) | -11.0 Percent change | Standard Deviation 56.61 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 18 (n=26,25) | -7.6 Percent change | Standard Deviation 40.35 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 60 (n=8,8) | -24.5 Percent change | Standard Deviation 31.89 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 69 (n=3,5) | -13.4 Percent change | Standard Deviation 42.68 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 63 (n=6,7) | -28.6 Percent change | Standard Deviation 31.2 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 21 (n=21,25) | -12.1 Percent change | Standard Deviation 34.23 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 72 (n=3,4) | -4.5 Percent change | Standard Deviation 40.94 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 9 (n=46,48) | -5.4 Percent change | Standard Deviation 33.49 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 75 (n=2,3) | -63.3 Percent change | Standard Deviation 41.13 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 0.5 (n=77,76) | -4.0 Percent change | Standard Deviation 28.23 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 24 (n=18,22) | -17.9 Percent change | Standard Deviation 43.46 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 1 (n=78,72) | -7.3 Percent change | Standard Deviation 30.13 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 78 (n=1,1) | 14.5 Percent change | — |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 1.5 (n=75,71) | -5.5 Percent change | Standard Deviation 27.65 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 27 (n=16,18) | -9.0 Percent change | Standard Deviation 41.71 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 2 (n=73,67) | -0.7 Percent change | Standard Deviation 35.81 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 2.5 (n=70,67) | -3.3 Percent change | Standard Deviation 31.4 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 4 (n=68,61) | -6.9 Percent change | Standard Deviation 31.88 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 33 (n=13,15) | -9.5 Percent change | Standard Deviation 44.64 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 5 (n=62,58) | -4.3 Percent change | Standard Deviation 36.96 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 36 (n=10,13) | -12.7 Percent change | Standard Deviation 65.43 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 6 (n=59,57) | -5.6 Percent change | Standard Deviation 34.28 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 3 (n=70,67) | -2.6 Percent change | Standard Deviation 35.79 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 7 (n=52,53) | -9.8 Percent change | Standard Deviation 34.44 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 39 (n=10,12) | -26.6 Percent change | Standard Deviation 42.89 |
| Pasireotide 600 ug | Percent Change From Baseline in Serum Cortisol | month 8 (n=50,46) | -10.2 Percent change | Standard Deviation 30.85 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 2 (n=73,67) | -6.4 Percent change | Standard Deviation 29.75 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 2.5 (n=70,67) | -10.1 Percent change | Standard Deviation 31.23 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 3 (n=70,67) | -10.2 Percent change | Standard Deviation 25.6 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 8 (n=50,46) | -9.9 Percent change | Standard Deviation 35.79 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 9 (n=46,48) | -5.8 Percent change | Standard Deviation 31.56 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 30 (n=14,19) | -22.7 Percent change | Standard Deviation 32.46 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 33 (n=13,15) | -25.2 Percent change | Standard Deviation 25.96 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 63 (n=6,7) | -24.0 Percent change | Standard Deviation 26.41 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 66 (n=4,6) | -22.5 Percent change | Standard Deviation 36.19 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 75 (n=2,3) | -23.2 Percent change | Standard Deviation 25.71 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 78 (n=1,1) | -53.3 Percent change | — |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 10 (n=42,47) | -9.3 Percent change | Standard Deviation 28.39 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 11 (n=41,41) | -14.0 Percent change | Standard Deviation 29.63 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 12 (n=39,38) | -15.2 Percent change | Standard Deviation 21.99 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 15 (n=26,26) | -12.5 Percent change | Standard Deviation 29.27 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 18 (n=26,25) | -17.8 Percent change | Standard Deviation 28.39 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 21 (n=21,25) | -15.5 Percent change | Standard Deviation 34.94 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 24 (n=18,22) | -18.1 Percent change | Standard Deviation 34.27 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 27 (n=16,18) | -12.7 Percent change | Standard Deviation 28.53 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 36 (n=10,13) | -13.3 Percent change | Standard Deviation 37.84 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 39 (n=10,12) | -25.9 Percent change | Standard Deviation 33.15 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 42 (n=10,12) | -18.1 Percent change | Standard Deviation 35.25 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 45 (n=10,11) | -8.5 Percent change | Standard Deviation 32.55 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 48 (n=9,11) | -20.1 Percent change | Standard Deviation 39.42 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 51 (n=9,9) | -24.0 Percent change | Standard Deviation 31.53 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 54 (n=9,9) | -6.8 Percent change | Standard Deviation 28.07 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 57 (n=8,8) | -30.8 Percent change | Standard Deviation 22.21 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 60 (n=8,8) | -18.9 Percent change | Standard Deviation 22.05 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 69 (n=3,5) | -33.6 Percent change | Standard Deviation 10.31 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 72 (n=3,4) | -22.7 Percent change | Standard Deviation 23.57 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 0.5 (n=77,76) | -10.8 Percent change | Standard Deviation 30.57 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 1 (n=78,72) | -7.7 Percent change | Standard Deviation 32 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 1.5 (n=75,71) | -7.1 Percent change | Standard Deviation 31.34 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 4 (n=68,61) | -10.8 Percent change | Standard Deviation 28.1 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 5 (n=62,58) | -10.8 Percent change | Standard Deviation 26.5 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 6 (n=59,57) | -9.3 Percent change | Standard Deviation 31.45 |
| Pasireotide 900 ug | Percent Change From Baseline in Serum Cortisol | month 7 (n=52,53) | -5.8 Percent change | Standard Deviation 26.35 |
Secondary
Time to First UFC Response
Time to first UFC response is defined as the number of months from baseline to first attainment of UFC response.
Time frame: 12 months
Population: Full Analysis Set (FAS): The full analysis set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pasireotide 600 ug | Time to First UFC Response | 1.0 months |
| Pasireotide 900 ug | Time to First UFC Response | 1.0 months |