Cushing's Disease
Conditions
Keywords
Cushing's disease, Hormone disorder, Cortisol, Adrenocorticotropic hormone, Pituitary tumor, SOM230, adult
Brief summary
This study provided access to pasireotide sc in patients with Cushing's disease.and provided additional information for safety and efficacy of pasireotide s.c.
Detailed description
Purpose of this study was to give access to pasireotide sc for patients with Cushing's disease as no medical treatment for Cushing's disease was approved at the time of the study initiation. The study population consisted of patients with persistent or recurrent Cushing's disease or patients with de novo Cushing's disease that were not considered candidates for pituitary surgery (poor surgery candidates, surgically unapproachable tumor, patients with no visible pituitary tumor, patients who refused surgery). A confirmed Cushing's disease diagnosis was required.
Interventions
DRUGPasireotide sub-cutaneous
Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg, 600 μg, or 300 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg and 600 μg for glucose impaired metabolism patients
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained prior to any screening procedures 2. Male or female patients aged 18 years or greater 3. Patients with confirmed diagnosis of Cushing's disease as evidenced by mean urinary free cortisol of three 24-hour urine samples collected during the 3-week screening period above the upper limit of the laboratory normal range morning plasma ACTH within the normal or above normal range either MRI confirmation of pituitary adenoma (greater than or equal to 0.6 cm), or inferior petrosal sinus gradient \>3 after CRH stimulation for those patients with a microadenoma less than 0.6 cm, or for patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma. 4. Patients with de novo Cushing's disease must not be considered as candidates for pituitary surgery (i.e. poor surgical candidates, surgically unapproachable tumors, patients with no visible pituitary tumor, patients who refuse to have surgical treatment) 5. Karnofsky performance status \>60 (i.e. requires occasional assistance, but is able to care for most of his personal needs) 6. For patients on previous medical treatment for Cushing's disease the following washout periods must be completed before screening assessments are performed * Inhibitors of steroidogenesis (e.g. ketoconazole, metyrapone, rosiglitazone): 1 week * Dopamine agonists (e.g. bromocriptine, cabergoline): 4 weeks * Mitotane: 6 months * Octreotide LAR and Lanreotide autogel: 8 weeks * Lanreotide SR: 4 weeks * Octreotide (immediate release formulation): 1 week * Glucocorticoid receptor inhibitor (mifepristone): 4 weeks
Exclusion criteria
1. Radiotherapy of the pituitary \<4 weeks before screening or patient who has not recovered from side effects 2. Patients with compression of the optic chiasm causing acute clinically significant visual field defect 3. Patients with Cushing's syndrome due to ectopic ACTH secretion 4. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia 5. Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1) 6. Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA) 7. Patients who have undergone major surgery within 1 month prior to screening 8. Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis (patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be included) 9. Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C \>8% 10. Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade AV block, history of acute MI less than one year prior to study entry * QTcF \>450 msec at screening * History of syncope or family history of idiopathic sudden death * Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure * Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism, concomitant medication(s) with known risk for TdP 11. Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST more than 2 x ULN, serum creatinine \>2.0 x ULN, serum bilirubin \>1.5 x ULN, serum albumin \< 0.67 x LLN at screening 12. Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results, such as * History of immunocompromise, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed * Presence of active or suspected acute or chronic uncontrolled infection * History of, or current alcohol misuse/abuse in the 12 month period prior to screening 13. Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. If a woman is participating in the trial then one form of contraception is sufficient (pill or diaphragm) and the partner should use a condom. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to screening and must agree to continue the oral contraceptive throughout the course of the study and for one month after the study has ended. Male patients who are sexually active are required to use condoms during the study and for three month afterwards as a precautionary measure (available data do not suggest any increased reproductive risk with the study drugs) 14. Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to screening or patients who have previously been treated with pasireotide 15. Known hypersensitivity to somatostatin analogues 16. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study 17. Patients with presence of Hepatitis B surface antigen (HbsAg) 18. Patients with presence of Hepatitis C antibody test (anti-HCV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Baseline up to approximately 256 weeks | Only AEs occurring on or after the start of study treatment and no more than 28 days after the discontinuation of study treatment. A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. A patient with multiple severity grades for an AE while on a treatment, is only counted under the maximum grade. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Baseline, week 12, 24 and 48 | The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory. |
| Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Baseline, week 12, 24 and 48 | The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory. |
| Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Baseline, week 12, 24 and 48 | A 12-item Cushing's syndrome HRQoL questionnaire (CushingQoL, cf. Webb et al 2008) was implemented and patients who completed 9 or more items at a visit were considered evaluable for that visit. The standardized scores were calculated as follows: 1) Obtain raw scores, denoted by X, as the sum of all the ratings on all the HRQoL questions for a single patient and the score can range from 12 (worst HRQoL) to 60 points (best HRQoL). Therefore, the lower the score, greater the negative impact on HRQoL and 2) obtain standardized score, Y, for a single patient • Y = 100 (X-12) / (60-12) = 100 (X-12)/48. For example, if a patient answers all 12 items with 'Sometimes' or 'Somewhat', X = 36 and Y = 100 ∙ 24/48 = 50 The WPAI-GH questionnaire was used to assess work productivity and activity impairment. However, there was very limited baseline data and therefore the results and outcomes of the objective, 'change from baseline in WPAI-GH scores' are not included. |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Baseline, week 12, 24 and 48 | Standing systolic and diastolic BP based on 1 assessment and sitting systolic and diastolic BP was mean of 3 assessments. |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Baseline, week 12, 24 and 48 | Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100 |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Baseline week 12, 24 and 48 | degrees celius |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Baseline, week 12, 24 and 48 | Percent change in patients reducing by at least one class level. Class levels: \<25.0, 25.0 to \<30.0, ≥ 30.0. Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100 |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Baseline, week 12, 24 and 48 | Direct observation of ability to stand unaided: 0=able to stand easily with arms extended, 1=able to stand after several efforts without using arms as assistance, 2=able to stand only by using arms as assistance 3=completely unable to stand |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Baseline, week 12, 24 and 48 | Clinically relevant threshold (at any time point). Reduction of ≥ 5%, Reduction of ≥ 10% |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Baseline, week 12, 24 and 48 | Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100. Ferriman-Gallway scoring was used: 0=minimum and 36 was maximum in females only. |
| Percent Change From Baseline in Growth Hormone (GH) Values | Baseline, week 12, 24 and 48 | Descriptive summary of the effect of pasireotide on GH. |
| Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Baseline, week 12, 24 and 48 | Descriptive summary of the effect of pasireotide on IGF-1 |
| Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Baseline, week 12, 24 and 48 | Clinically relevant threshold (at any time point) was reduction of ≥ 5% |
Countries
Brazil, Czechia, Germany, Greece, Lebanon, Romania, Russia, South Korea, Spain, Thailand, United States
Participant flow
Pre-assignment details
After a 21-day screening period, patients who met the inclusion/exclusion criteria received pasireotide subcutaneous twice a day (BID)
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide 600 μg Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 600 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 600 μg for glucose impaired metabolism patients. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 600 μg bid group includes all patients whose mean daily dose \< 1500 μg /day. | 49 |
| Pasireotide 900 μg Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg. Mean daily dose category is defined on the mean daily dose considering the following grouping rule: 900 μg bid group includes all patients whose mean daily dose ≥ 1500 μg /day | 55 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 | 0 |
| Overall Study | Adverse Event | 12 | 8 |
| Overall Study | condition no longer requires study drug | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 23 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 4 |
Baseline characteristics
| Characteristic | Pasireotide 900 μg | Total | Pasireotide 600 μg |
|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 12.55 | 42.5 years STANDARD_DEVIATION 13.07 | 45.5 years STANDARD_DEVIATION 13.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 21 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 36 Participants | 75 Participants | 39 Participants |
| Sex: Female, Male Female | 47 Participants | 84 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 20 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 1 / 55 | 1 / 104 |
| other Total, other adverse events | 49 / 49 | 54 / 55 | 103 / 104 |
| serious Total, serious adverse events | 13 / 49 | 17 / 55 | 30 / 104 |
Outcome results
Primary
Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE)
Only AEs occurring on or after the start of study treatment and no more than 28 days after the discontinuation of study treatment. A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. A patient with multiple severity grades for an AE while on a treatment, is only counted under the maximum grade.
Time frame: Baseline up to approximately 256 weeks
Population: Three additional arms were created to display subset of subjects with specific criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 2.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 2.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 18.4 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 2.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 8.2 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 2.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 53.1 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 6.1 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 2.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 26.5 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 4.1 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 6.1 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 53.1 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 26.5 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 18.4 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 8.2 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 2.0 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 4.1 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 2.0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 1.8 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 5.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 1.8 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 12.7 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 29.1 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 7.3 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 3.6 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 0 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 7.3 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 1.8 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 27.3 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 10.9 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 3.6 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 5.5 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 0 percentage of participants |
| 900 μg - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 1.9 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 2.9 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 3.8 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 5.8 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 12.5 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 40.4 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 19.2 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 1.0 percentage of participants |
| All Patients - All Grades | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Ear and labyrinth disorders | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Endocrine disorders | 2.9 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Infections and infestations | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Hepatobiliary disorders | 3.8 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Any primary system organ class | 39.4 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Psychiatric disorders | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Musculoskeletal and connective tissue disorders | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gen disorders,admin site conditions | 1.9 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Investigations | 5.8 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Nervous system disorders | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Respiratory, thoracic, mediastinal disorders | 0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Metabolism and nutrition disorders | 18.3 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Neoplasms benign, malignant and unspecified | 1.0 percentage of participants |
| All Patients - Grades 3/4 | Percentage of Patients With a Drug-related Adverse Event That is Recorded as Grade 3 or 4 or as a Serious Adverse Event (SAE) | Gastrointestinal disorders | 12.5 percentage of participants |
Secondary
Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline
The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory.
Time frame: Baseline, week 12, 24 and 48
Population: LOCF Week 24: last available mean 24h-UFC of at least two samples between and including week 12 and week 24; LOCF Week 48: last available mean 24h-UFC of at least two samples between and including week 12 and week 48. Two-sided 95% confidence intervals for proportions are calculated using the exact method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 600 µg Bid - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 (LOCF) | 56.8 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 12 | 74.1 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 | 68.2 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 | 60.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 (LOCF) | 51.4 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 | 33.3 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 (LOCF) | 42.9 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 | 54.5 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 (LOCF) | 38.8 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 12 | 48.7 percentage of participants |
| 900 μg - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 12 | 59.1 percentage of participants |
| 900 μg - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 | 50.00 percentage of participants |
| 900 μg - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 24 (LOCF) | 46.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 (LOCF) | 46.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients Achieving a Reduction of Mean UFC ≥ 50% From Baseline | Week 48 | 57.1 percentage of participants |
Secondary
Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN)
The 24h-UFC concentration results from three samples during screening were averaged to obtain baseline. After baseline, mean 24h UFC was determined at week 24. At Week 4, 8, 16 and 20, mean 24h UFC was determined from two 24 hour urine collections collected on two consecutive days occurring before the visit. At Week 12, 24 and 48, the mean 24h-UFC from three 24 hour urine collections, collected over the week before the visit, was determined. After Week 24, the mean 24h UFC was determined at 12-week intervals until end of study visit, from two 24 hour collections during two consecutive days prior to each respective visit (except at Week 48). UFC was determined by liquid chromatography tandem mass spectroscopy (LC/MS/MS). The normal ranges were determined by the central laboratory's own reference range. All samples, including screening samples, were analyzed by a central laboratory.
Time frame: Baseline, week 12, 24 and 48
Population: LOCF Week 24: last available mean 24h-UFC of at least two samples between and including week 12 and week 24; LOCF Week 48: last available mean 24h-UFC of at least two samples between and including week 12 and week 48. Two-sided 95% confidence intervals for proportions are calculated using the exact method
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 600 µg Bid - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 (LOCF) | 54.1 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 12 | 77.8 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 | 68.2 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 | 70.0 percentage of participants |
| 600 µg Bid - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 (LOCF) | 51.4 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 | 29.2 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 (LOCF) | 22.4 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 | 18.2 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 (LOCF) | 28.6 percentage of participants |
| 600 μg - Grades 3/4 | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 12 | 38.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 12 | 54.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 | 47.8 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 24 (LOCF) | 39.5 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 (LOCF) | 34.9 percentage of participants |
| 900 μg - All Grades | Percentage of Patients With Mean Urinary Free Cortisol (UFC) ≤ Upper Limit of Normal (ULN) | Week 48 | 42.9 percentage of participants |
Secondary
Percent Change From Baseline in Growth Hormone (GH) Values
Descriptive summary of the effect of pasireotide on GH.
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 24 | -22.2 percent change of µg/L | Standard Deviation 62.43 |
| 600 µg Bid - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 12 | -17.3 percent change of µg/L | Standard Deviation 109.89 |
| 600 µg Bid - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 48 | 23.1 percent change of µg/L | Standard Deviation 127.3 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Growth Hormone (GH) Values | Week 24 | -26.2 percent change of µg/L | Standard Deviation 105.44 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Growth Hormone (GH) Values | Week 12 | -20.90 percent change of µg/L | Standard Deviation 156.6 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Growth Hormone (GH) Values | Week 48 | -1.0 percent change of µg/L | Standard Deviation 134.97 |
| 900 μg - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 12 | -19.3 percent change of µg/L | Standard Deviation 137.33 |
| 900 μg - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 48 | 9.7 percent change of µg/L | Standard Deviation 130.32 |
| 900 μg - All Grades | Percent Change From Baseline in Growth Hormone (GH) Values | Week 24 | -24.4 percent change of µg/L | Standard Deviation 88.7 |
Secondary
Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values
Descriptive summary of the effect of pasireotide on IGF-1
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 24 | -49.2 percent change of ng/ml | Standard Deviation 26.56 |
| 600 µg Bid - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 12 | -53.4 percent change of ng/ml | Standard Deviation 23.66 |
| 600 µg Bid - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 48 | -41.8 percent change of ng/ml | Standard Deviation 35.72 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 24 | -56.2 percent change of ng/ml | Standard Deviation 26.55 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 12 | -57.8 percent change of ng/ml | Standard Deviation 23.93 |
| 600 μg - Grades 3/4 | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 48 | -52.1 percent change of ng/ml | Standard Deviation 21.87 |
| 900 μg - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 12 | -55.9 percent change of ng/ml | Standard Deviation 23.76 |
| 900 μg - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 48 | -47.6 percent change of ng/ml | Standard Deviation 28.71 |
| 900 μg - All Grades | Percent Change From Baseline in Insulin Growth Factor - 1 (IGF - 1) Values | Week 24 | -53.1 percent change of ng/ml | Standard Deviation 26.53 |
Secondary
Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores
A 12-item Cushing's syndrome HRQoL questionnaire (CushingQoL, cf. Webb et al 2008) was implemented and patients who completed 9 or more items at a visit were considered evaluable for that visit. The standardized scores were calculated as follows: 1) Obtain raw scores, denoted by X, as the sum of all the ratings on all the HRQoL questions for a single patient and the score can range from 12 (worst HRQoL) to 60 points (best HRQoL). Therefore, the lower the score, greater the negative impact on HRQoL and 2) obtain standardized score, Y, for a single patient • Y = 100 (X-12) / (60-12) = 100 (X-12)/48. For example, if a patient answers all 12 items with 'Sometimes' or 'Somewhat', X = 36 and Y = 100 ∙ 24/48 = 50 The WPAI-GH questionnaire was used to assess work productivity and activity impairment. However, there was very limited baseline data and therefore the results and outcomes of the objective, 'change from baseline in WPAI-GH scores' are not included.
Time frame: Baseline, week 12, 24 and 48
Population: Only patients who completed at least 9 questions on questionnaire were included for that visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 48 | 24.0 percent change in score | Standard Deviation 37.76 |
| 600 µg Bid - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 12 | 21.3 percent change in score | Standard Deviation 47.03 |
| 600 µg Bid - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 24 | 36.7 percent change in score | Standard Deviation 59.25 |
| 600 μg - Grades 3/4 | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 48 | 42.3 percent change in score | Standard Deviation 60.75 |
| 600 μg - Grades 3/4 | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 12 | 100.8 percent change in score | Standard Deviation 252.25 |
| 600 μg - Grades 3/4 | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 24 | 119.7 percent change in score | Standard Deviation 321.61 |
| 900 μg - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 48 | 34.4 percent change in score | Standard Deviation 52.29 |
| 900 μg - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 12 | 67.1 percent change in score | Standard Deviation 197.09 |
| 900 μg - All Grades | Percent Change in Cushing Quality of Life and Work Productivity and Activity Impairment-General Health (WPAI-GH) Scores | Week 24 | 82.3 percent change in score | Standard Deviation 243.19 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP)
Standing systolic and diastolic BP based on 1 assessment and sitting systolic and diastolic BP was mean of 3 assessments.
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 12 | -6.8 percent change of mmhg | Standard Deviation 12.04 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 24 | -7.4 percent change of mmhg | Standard Deviation 8.97 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 48 | -5.1 percent change of mmhg | Standard Deviation 8.57 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 12 | -7.9 percent change of mmhg | Standard Deviation 12.49 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 24 | -10.9 percent change of mmhg | Standard Deviation 10.3 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 48 | -6.5 percent change of mmhg | Standard Deviation 9.45 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 12 | -4.6 percent change of mmhg | Standard Deviation 15.13 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 24 | -6.2 percent change of mmhg | Standard Deviation 7.29 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 48 | -3.3 percent change of mmhg | Standard Deviation 10.38 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 12 | -5.5 percent change of mmhg | Standard Deviation 16.02 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 24 | -7.6 percent change of mmhg | Standard Deviation 10.3 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 48 | -2.1 percent change of mmhg | Standard Deviation 13.78 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 48 | -4.4 percent change of mmhg | Standard Deviation 14.13 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 12 | -1.4 percent change of mmhg | Standard Deviation 14.4 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 12 | -0.2 percent change of mmhg | Standard Deviation 14.4 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 48 | -4.3 percent change of mmhg | Standard Deviation 13.93 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 24 | -5.7 percent change of mmhg | Standard Deviation 11.09 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 48 | -4.4 percent change of mmhg | Standard Deviation 13.86 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 24 | -5.3 percent change of mmhg | Standard Deviation 16.74 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 48 | -4.7 percent change of mmhg | Standard Deviation 12.55 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 24 | -3.8 percent change of mmhg | Standard Deviation 15.83 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 24 | -6.7 percent change of mmhg | Standard Deviation 14.09 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 12 | -3.6 percent change of mmhg | Standard Deviation 15.38 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 12 | -1.9 percent change of mmhg | Standard Deviation 17.63 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 12 | -5.5 percent change of mmhg | Standard Deviation 14.27 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 24 | -8.6 percent change of mmhg | Standard Deviation 12.62 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 12 | -3.5 percent change of mmhg | Standard Deviation 16.93 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing systolic Week 48 | -5.3 percent change of mmhg | Standard Deviation 12.1 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 12 | -2.1 percent change of mmhg | Standard Deviation 14.79 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 24 | -4.9 percent change of mmhg | Standard Deviation 12.65 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 24 | -6.3 percent change of mmhg | Standard Deviation 14.18 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 12 | -3.8 percent change of mmhg | Standard Deviation 13.61 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 24 | -6.5 percent change of mmhg | Standard Deviation 10.13 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting diastolic Week 48 | -3.8 percent change of mmhg | Standard Deviation 12.37 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Sitting systolic Week 48 | -4.9 percent change of mmhg | Standard Deviation 10.87 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Blood Pressure (BP) | Standing diastolic Week 48 | -3.4 percent change of mmhg | Standard Deviation 13.83 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI)
Percent change in patients reducing by at least one class level. Class levels: \<25.0, 25.0 to \<30.0, ≥ 30.0. Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 24 | -7.3 percent change in kg/m2 | Standard Deviation 5.46 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 12 | -4.2 percent change in kg/m2 | Standard Deviation 3.7 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 48 | -8.0 percent change in kg/m2 | Standard Deviation 6.82 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 24 | -5.2 percent change in kg/m2 | Standard Deviation 6.51 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 12 | -4.8 percent change in kg/m2 | Standard Deviation 5.38 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 48 | -6.3 percent change in kg/m2 | Standard Deviation 7.88 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 12 | -4.5 percent change in kg/m2 | Standard Deviation 4.69 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 48 | -7.0 percent change in kg/m2 | Standard Deviation 7.39 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Body Mass Index (BMI) | Week 24 | -6.1 percent change in kg/m2 | Standard Deviation 6.1 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism
Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100. Ferriman-Gallway scoring was used: 0=minimum and 36 was maximum in females only.
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 24 | -21.2 percent change in scores | Standard Deviation 32.72 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 12 | -12.2 percent change in scores | Standard Deviation 24.57 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 48 | -18.2 percent change in scores | Standard Deviation 30.12 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 24 | -16.2 percent change in scores | Standard Deviation 46.99 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 12 | -8.2 percent change in scores | Standard Deviation 35.3 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 48 | 9.6 percent change in scores | Standard Deviation 143.83 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 12 | -10.0 percent change in scores | Standard Deviation 30.88 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 48 | -2.2 percent change in scores | Standard Deviation 110.2 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Hirsutism | Week 24 | 18.4 percent change in scores | Standard Deviation 40.79 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength
Direct observation of ability to stand unaided: 0=able to stand easily with arms extended, 1=able to stand after several efforts without using arms as assistance, 2=able to stand only by using arms as assistance 3=completely unable to stand
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 24 | -28.6 percent change in scores | Standard Deviation 48.8 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 12 | -34.6 percent change in scores | Standard Deviation 62.53 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 48 | -30.0 percent change in scores | Standard Deviation 44.72 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 24 | -47.6 percent change in scores | Standard Deviation 50.4 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 12 | -53.7 percent change in scores | Standard Deviation 46.98 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 48 | -75.0 percent change in scores | Standard Deviation 50 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 12 | -42.4 percent change in scores | Standard Deviation 56.28 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 48 | -50.0 percent change in scores | Standard Deviation 50 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Muscle Strength | Week 24 | -38.1 percent change in scores | Standard Deviation 48.67 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse
Change from baseline is shown as: Percent change from baseline (BL) =((Post BL value - BL value)/ BL value)\*100
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 48 | 2.9 percent change in bpm | Standard Deviation 16.39 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 24 | -1.8 percent change in bpm | Standard Deviation 17.05 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 12 | 2.3 percent change in bpm | Standard Deviation 18.93 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 48 | 3.7 percent change in bpm | Standard Deviation 15.46 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 12 | -7.5 percent change in bpm | Standard Deviation 11.5 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 24 | -2.6 percent change in bpm | Standard Deviation 18.07 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 24 | -2.2 percent change in bpm | Standard Deviation 17.46 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 12 | -3.2 percent change in bpm | Standard Deviation 15.87 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Pulse | Sitting pulse Week 48 | 3.3 percent change in bpm | Standard Deviation 15.65 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature
degrees celius
Time frame: Baseline week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 24 | -0.1 percent change in celius | Standard Deviation 1.15 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 12 | 0.1 percent change in celius | Standard Deviation 1.26 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 48 | 0.03 percent change in celius | Standard Deviation 1.47 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 24 | -0.1 percent change in celius | Standard Deviation 1.26 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 12 | -0.3 percent change in celius | Standard Deviation 1.06 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 48 | -0.1 percent change in celius | Standard Deviation 1.19 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 12 | -0.1 percent change in celius | Standard Deviation 1.17 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 48 | 0.1 percent change in celius | Standard Deviation 1.31 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Temperature | Week 24 | -0.1 percent change in celius | Standard Deviation 1.2 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference
Clinically relevant threshold (at any time point). Reduction of ≥ 5%, Reduction of ≥ 10%
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 24 | -5.8 percent change of centimeters | Standard Deviation 6.28 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 12 | -2.0 percent change of centimeters | Standard Deviation 4.29 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 48 | -5.1 percent change of centimeters | Standard Deviation 5.74 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 24 | -3.1 percent change of centimeters | Standard Deviation 5.48 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 12 | -2.9 percent change of centimeters | Standard Deviation 6.7 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 48 | -4.1 percent change of centimeters | Standard Deviation 5.64 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 12 | -2.5 percent change of centimeters | Standard Deviation 5.72 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 48 | -4.6 percent change of centimeters | Standard Deviation 5.62 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Waist Circumference | Week 24 | -4.4 percent change of centimeters | Standard Deviation 5.96 |
Secondary
Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight
Clinically relevant threshold (at any time point) was reduction of ≥ 5%
Time frame: Baseline, week 12, 24 and 48
Population: Number of patients with available data differed at visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 24 | -7.3 percent change in kg | Standard Deviation 5.46 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 12 | -4.2 percent change in kg | Standard Deviation 3.7 |
| 600 µg Bid - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 48 | -8.0 percent change in kg | Standard Deviation 6.82 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 24 | -5.2 percent change in kg | Standard Deviation 6.51 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 12 | -4.8 percent change in kg | Standard Deviation 5.38 |
| 600 μg - Grades 3/4 | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 48 | -6.3 percent change in kg | Standard Deviation 7.88 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 12 | -4.5 percent change in kg | Standard Deviation 4.69 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 48 | -7.0 percent change in kg | Standard Deviation 7.39 |
| 900 μg - All Grades | Percent Change in Cushing's Disease Clinical Signs and Symptoms - Weight | Week 24 | -6.1 percent change in kg | Standard Deviation 6.1 |