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Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

Primary Purpose

Cushings Disease

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Pasireotide with or without cabergoline

About this trial

This is an interventional treatment trial for Cushings Disease focused on measuring pituitary tumors, pasireotide, cabergoline, combination treatment, UFC, hormone disorder, cortisol, adrenocorticotropic hormone, Cushing Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Written informed consent obtained prior to screening procedures
Adult patients with confirmed diagnosis of ACTH-dependent Cushing's disease as evidenced by all of the following:
1. The mean of three 24-hour urine samples collected within 2 weeks > 1xULN with 2 out of 3 samples >ULN
2. Morning plasma ACTH within the normal or above normal range
3. Either MRI confirmation of pituitary adenoma > 6 mm, or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a tumor less than or equal to 6 mm*. For patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma *If IPSS had previously been performed without CRH (e.g. with DDAVP), then a central to peripheral pre-stimulation gradient > 2 was required. If IPSS had not previously been performed, IPSS with CRH stimulation was required.
Patients with de novo Cushing's disease could only be included only if they were not considered candidates for pituitary surgery (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refused to have surgical treatment)
Male or female patients aged 18 years or greater
Karnofsky performance status ≥ 60 (i.e. required occasional assistance, but was able to care for most of their personal needs)
Patients on medical treatment for Cushing's disease the following washout periods must have been completed before screening assessments were performed
- Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week
- Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPARγ agonists (rosiglitazone or pioglitazone): 4 weeks
- Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks
- Octreotide (immediate release formulation): 1 week
- Progesterone receptor antagonist (mifepristone): 4 weeks
Patients could have been considered to enter the trial if they met any one of the following criteria: 1) They were naive to pasireotide 2) They had received pasireotide in the past and have been discontinued because of lack of efficacy (2 weeks for washout prior to screening for patients treated with pasireotide subcutaneously and 12 weeks of washout prior to screening for patients treated with pasireotide LAR) 3) Patients who were on maximal tolerated dose but had not achieved biochemical control
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they were using highly effective methods of contraception during dosing and for 30 days after stopping study medication.
Male participants in the trial must have agreed to use a condom during intercourse, and not to father a child during the study and for the period of 30 days following stopping of the study treatment.

Exclusion criteria:

Patients with compression of the optic chiasm that caused any visual field defect that required surgical intervention
Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >450 ms in males, and > 460 ms in females. hypokalemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval.
Patients with clinically significant valvular disease.
Patients with Cushing's syndrome due to ectopic ACTH secretion
Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
Patients who had congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function
Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2 X ULN, serum bilirubin >2.0 X ULN
Patients with serum creatinine >2.0 X ULN
Patients with WBC <3 X 10e9/L; Hb 90% < LLN; PLT <100 X 10e9/L
Patients with presence of Hepatitis B surface antigen (HbsAg)
Patients with presence of Hepatitis C antibody test (anti-HCV)
Patients with severe hepatic impairment (Child Pugh C) and hypersensitivity to pasireotide or cabergoline
Patients with lung, pericardial, and retroperitoneal fibrosis; gastro-duodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynauds syndrome.
Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)
Patients with end-stage renal failure and/or hemodialysis
Patients with presence of active or suspected acute or chronic uncontrolled infection
Patients with a history of non-complance to medical regimens or who were considered potentially unreliable or were unable to complete the entire study
Patients with presence of Hepatitis B surface antigen (HbsAg)
Patients with presence of Hepatitis C antibody test (anti-HCV)
Patients with severe hepatic impairment (Child Pugh C) and hpersensitivity to pasireotide or cabergoline
Patients with lung, pericardial, and retroperitoneal fibrosis; gastroduodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynaud's syndrome
Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5mIU/mL)
Patients with end-stage renal failure and/or hemodialysis

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pasireotide +/- cabergoline

Arm Description

pasireotide alone or with cabergoline

Outcomes

Primary Outcome Measures

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35

Participants who attained mUFC ≤ 1.0 x ULN (upper limit of normal) with pasireotide alone or in combination with cabergoline. The 24h-UFC concentration results from three samples, collected during the screening period, were averaged to obtain the Baseline urinary free cortisol level. mean 24h-UFC was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit. Imputation: subjects who completed the end of treatment visit at Week 35, but had missing evaluation of mean urinary free cortisol (mUFC). The last available mUFC assessment at or after previous visit (week) before last week was carried forward as the last week mUFC assessment.

Secondary Outcome Measures

Mean Urinary Free Cortisol (mUFC) at Scheduled Visits

Mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Duration (Weeks) of Controlled or Partially Controlled Response

Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC ≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN and the reduction from baseline falls to less than 50% from the first time

Plasma Adrenocorticotropic Hormone (ACTH)

A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.

Serum Cortisol Levels

A pre-dose blood draw for an 8 am fasting serum cortisol measurement were taken at visits. Samples were analyzed by a central laboratory.

Sitting Systolic Blood Pressure at Week 35

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Sitting Diastolic Blood Pressure at Week 35

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Body Weight at Week 35

Weight was was one of the measures of clinical symptoms of CD

Body Mass Index at Week 35

Body mass index was one of the measurements of clinical symptoms of CD. Body mass index=weight in kg divided by the square of the body height (in meters)

Waist Circumference at Week 35

Waist circumference was one of the measurements of clinical signs of CD

LDL, HDL and Total Cholesterol at Week 35

LDL=Low density lipoprotein, HDL=high density llipoprotein and total protein were analyzed by a central laboratory

Mean Scores of Cushing QoL Standardized Score at Week 17 and 35

Patients who completed nine or more items for the 12-item Cushing's syndrome QoL questionaire were considered evaluable for that assessment. Raw scores were obtained for the 12 items using the following scoring: 1) always or very much, 2) often or quite a bit, 3) sometimes or somewhat, 4) rarely or very little, 5) never or not at all. Then the standardized score, Y, was calculated for each patient as follows: Y = 100* (X - n) / n*5 - n*1) = 100 * (X - n) / 4*n where X denoted the raw score and n the number of questions answered by the patient. The higher the score, the better the QoL. The best possible standardized score was 100 and the worst possible standardized score was 0

Mean Scores of SF-12v2 Domain Scores at Week 17 and 35

SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Facial Rubor

Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Hirsutism

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Striae

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Supraclavicular Fat Pad

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Dorsal Fat Pad

Number of Participants With Shift From Mild to Severe in Clinical Signs of Hypercortisolism

Facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad were assessed. Two photographs, one frontal and one lateral from the shoulders up will be taken to assess facial plethora, supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position will be taken to assess striae, and hirsutism. The photographs must be assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline

Number of Patients With Shift From Standing Easily to Not Being Able to Stand

To test proximal muscle strength patients should be placed in a low seated position (for instance on an examination room stool). They should be asked to extend the arms in front of them. From this seated position patients will be asked to stand up. Patients will be evaluated using the following scale: 3. - completely unable to stand 2. - able to stand only by using arms as assistance 1. - able to stand after several efforts without using arms as assistance 0. - able to stand easily with arms extended

Full Information

NCT ID

NCT01915303

First Posted

June 10, 2013

Last Updated

August 28, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01915303

Brief Title

Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

Official Title

A Phase II Trial to Assess the Efficacy and Safety of Pasireotide s.c. Alone or in Combination With Cabergoline in Patients With Cushing's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Terminated

Study Start Date

March 6, 2014 (Actual)

Primary Completion Date

September 5, 2016 (Actual)

Study Completion Date

September 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The main purpose of this prospective, multicenter, open-label phase II study, was to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing's disease.

Detailed Description

This was an open-label, multi-center, international, non-comparative study with adult patients with confirmed diagnosis of Cushing's disease. Given the fact that CD patients may need a multimodality treatment approach, the trial design aimed to mimic CD treatment by using a medical stepwise approach. Therefore, the whole patient population started treatment with Pasireotide and only in patients within this population who did not achieve biochemical control, cabergoline was added. The whole patient population had never received pasireotide or had received it in the past (reasons of discontinuation not related to safety). Core Phase Pasireotide naïve patients started pasireotide monotherapy at the dose of 0.6 mg s.c. bid. If at the end of the 8 week treatment period, the biochemical control was not achieved and the 0.6mg bid dose was well tolerated, the pasireotide dose was increased to 0.9mg bid. If the 0.9mg bid dose of pasireotide did not lead to biochemical control, cabergoline was added with a starting dose of 0.5mg qd. If the combination dose of 0.9mg bid of pasireotide plus 0.5mg qd cabergolinedid not achieve biochemical control, the cabergoline dose will be increased to 1.0mg qd. Patients who were currently being treated with maximal tolerated doses of pasireotide monotherapy for at least 8 weeks at screening without achieving normal mUFC, entered the study with a combination therapy starting with cabergoline 0.5mg qd. Extension Phase • After 35 weeks of treatment in core phase, patients had the option to continue study treatment if pasireotide was not yet approved for commercial use and/or reimbursed - if country reimbursement was applicable - in each respective country, or until 31st December 2017, or once an applicable roll over protocol became available, or whichever occurred first. Novartis had a local transition plan in order to ensure that all trial patients had access to the study medication without any delay in their treatment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cushings Disease

Keywords

pituitary tumors, pasireotide, cabergoline, combination treatment, UFC, hormone disorder, cortisol, adrenocorticotropic hormone, Cushing Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

68 (Actual)

8. Arms, Groups, and Interventions

Arm Title

pasireotide +/- cabergoline

Arm Type

Experimental

Arm Description

pasireotide alone or with cabergoline

Intervention Type

Drug

Intervention Name(s)

Pasireotide with or without cabergoline

Intervention Description

The trial consisted of Pasireotide-untreated patients who started pasireotide 0.6mg twice a day for 8 weeks. If biochemical control was not achieved by the end of the 8 weeks, and the 0.6mg dose is well-tolerated, the dose was increased to 0.9mg twice a day for another 8 weeks. If biochemical control is not achieved, cabergoline was added and patients began combination treatment with cabergoline at the starting dose of 0.5mg once a day for 8 weeks. If biochemical control is still not achieved at the end of the third 8 week period, the dose of cabergoline was increased to 1.0mg once a day. Patients could also immediately start the combination treatment by adding cabergoline 0.5mg once a day at study entry to their current maximal tolerated dose of pasireotide. Patients continued with the combination treatment for 8 weeks. If biochemical control was not not achieved by the end of the 8 week period, the dose of cabergoline was increased to 1mg once a day.

Primary Outcome Measure Information:

Title

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35

Description

Time Frame

Baseline up to week 35

Secondary Outcome Measure Information:

Title

Mean Urinary Free Cortisol (mUFC) at Scheduled Visits

Description

Mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Title

Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN

Description

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Time Frame

Baseline up to week 235

Title

Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC

Description

Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.

Time Frame

Baseline up to week 235

Title

Duration (Weeks) of Controlled or Partially Controlled Response

Description

Time Frame

from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN

Title

Plasma Adrenocorticotropic Hormone (ACTH)

Description

A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Title

Serum Cortisol Levels

Description

A pre-dose blood draw for an 8 am fasting serum cortisol measurement were taken at visits. Samples were analyzed by a central laboratory.

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Title

Sitting Systolic Blood Pressure at Week 35

Description

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Time Frame

Baseline and week 35

Title

Sitting Diastolic Blood Pressure at Week 35

Description

The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures

Time Frame

Baseline and week 35

Title

Body Weight at Week 35

Description

Weight was was one of the measures of clinical symptoms of CD

Time Frame

Baseline and week 35

Title

Body Mass Index at Week 35

Description

Body mass index was one of the measurements of clinical symptoms of CD. Body mass index=weight in kg divided by the square of the body height (in meters)

Time Frame

Baseline and week 35

Title

Waist Circumference at Week 35

Description

Waist circumference was one of the measurements of clinical signs of CD

Time Frame

Baseline and week 35

Title

LDL, HDL and Total Cholesterol at Week 35

Description

LDL=Low density lipoprotein, HDL=high density llipoprotein and total protein were analyzed by a central laboratory

Time Frame

Baseline and week 35

Title

Mean Scores of Cushing QoL Standardized Score at Week 17 and 35

Description

Time Frame

Baseline and week 17 and 35

Title

Mean Scores of SF-12v2 Domain Scores at Week 17 and 35

Description

Time Frame

Baseline, week 17 and 35

Title

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Facial Rubor

Description

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

Title

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Hirsutism

Description

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

Title

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Striae

Description

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

Title

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Supraclavicular Fat Pad

Description

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Title

Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Dorsal Fat Pad

Description

Time Frame

Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension

Title

Number of Participants With Shift From Mild to Severe in Clinical Signs of Hypercortisolism

Description

Time Frame

Baseline, weeks 1, 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension

Title

Number of Patients With Shift From Standing Easily to Not Being Able to Stand

Description

Time Frame

Baseline up to week 267

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Written informed consent obtained prior to screening procedures Adult patients with confirmed diagnosis of ACTH-dependent Cushing's disease as evidenced by all of the following: The mean of three 24-hour urine samples collected within 2 weeks > 1xULN with 2 out of 3 samples >ULN Morning plasma ACTH within the normal or above normal range Either MRI confirmation of pituitary adenoma > 6 mm, or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a tumor less than or equal to 6 mm*. For patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma *If IPSS had previously been performed without CRH (e.g. with DDAVP), then a central to peripheral pre-stimulation gradient > 2 was required. If IPSS had not previously been performed, IPSS with CRH stimulation was required. Patients with de novo Cushing's disease could only be included only if they were not considered candidates for pituitary surgery (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refused to have surgical treatment) Male or female patients aged 18 years or greater Karnofsky performance status ≥ 60 (i.e. required occasional assistance, but was able to care for most of their personal needs) Patients on medical treatment for Cushing's disease the following washout periods must have been completed before screening assessments were performed Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPARγ agonists (rosiglitazone or pioglitazone): 4 weeks Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks Octreotide (immediate release formulation): 1 week Progesterone receptor antagonist (mifepristone): 4 weeks Patients could have been considered to enter the trial if they met any one of the following criteria: 1) They were naive to pasireotide 2) They had received pasireotide in the past and have been discontinued because of lack of efficacy (2 weeks for washout prior to screening for patients treated with pasireotide subcutaneously and 12 weeks of washout prior to screening for patients treated with pasireotide LAR) 3) Patients who were on maximal tolerated dose but had not achieved biochemical control Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they were using highly effective methods of contraception during dosing and for 30 days after stopping study medication. Male participants in the trial must have agreed to use a condom during intercourse, and not to father a child during the study and for the period of 30 days following stopping of the study treatment. Exclusion criteria: Patients with compression of the optic chiasm that caused any visual field defect that required surgical intervention Diabetic patients with poor glycemic control as evidenced by HbA1c >8% Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >450 ms in males, and > 460 ms in females. hypokalemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval. Patients with clinically significant valvular disease. Patients with Cushing's syndrome due to ectopic ACTH secretion Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia Patients who had congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2 X ULN, serum bilirubin >2.0 X ULN Patients with serum creatinine >2.0 X ULN Patients with WBC <3 X 10e9/L; Hb 90% < LLN; PLT <100 X 10e9/L Patients with presence of Hepatitis B surface antigen (HbsAg) Patients with presence of Hepatitis C antibody test (anti-HCV) Patients with severe hepatic impairment (Child Pugh C) and hypersensitivity to pasireotide or cabergoline Patients with lung, pericardial, and retroperitoneal fibrosis; gastro-duodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynauds syndrome. Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) Patients with end-stage renal failure and/or hemodialysis Patients with presence of active or suspected acute or chronic uncontrolled infection Patients with a history of non-complance to medical regimens or who were considered potentially unreliable or were unable to complete the entire study Patients with presence of Hepatitis B surface antigen (HbsAg) Patients with presence of Hepatitis C antibody test (anti-HCV) Patients with severe hepatic impairment (Child Pugh C) and hpersensitivity to pasireotide or cabergoline Patients with lung, pericardial, and retroperitoneal fibrosis; gastroduodenal ulcer or digestive haemorrhage, galactose intolerance, Parkinson's disease, uncontrolled hypertension and Raynaud's syndrome Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5mIU/mL) Patients with end-stage renal failure and/or hemodialysis

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of Alabama at Birmingham The Kirklin Clinic

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Oregon Health and Science University SOM230B2411

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Novartis Investigative Site

City

Caba

State/Province

Buenos Aires

ZIP/Postal Code

C1280AEB

Country

Argentina

Facility Name

Novartis Investigative Site

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Curitiba

State/Province

ZIP/Postal Code

80030-110

Country

Brazil

Facility Name

Novartis Investigative Site

City

Rio de Janeiro

State/Province

ZIP/Postal Code

21941-913

Country

Brazil

Facility Name

Novartis Investigative Site

City

Porto Alegre

State/Province

ZIP/Postal Code

90560-030

Country

Brazil

Facility Name

Novartis Investigative Site

City

Sao Paulo

State/Province

ZIP/Postal Code

05403 000

Country

Brazil

Facility Name

Novartis Investigative Site

City

Bogota

State/Province

Cundinamarca

ZIP/Postal Code

110111

Country

Colombia

Facility Name

Novartis Investigative Site

City

Vandoeuvre Cedex

ZIP/Postal Code

54511

Country

France

Facility Name

Novartis Investigative Site

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Novartis Investigative Site

City

Athens

ZIP/Postal Code

106 76

Country

Greece

Facility Name

Novartis Investigative Site

City

Thessaloniki

ZIP/Postal Code

GR 54636

Country

Greece

Facility Name

Novartis Investigative Site

City

Budapest

ZIP/Postal Code

1062

Country

Hungary

Facility Name

Novartis Investigative Site

City

Budapest

ZIP/Postal Code

1085

Country

Hungary

Facility Name

Novartis Investigative Site

City

Vellore

State/Province

Tamil Nadu

ZIP/Postal Code

632004

Country

India

Facility Name

Novartis Investigative Site

City

Chandigarh

ZIP/Postal Code

160 012

Country

India

Facility Name

Novartis Investigative Site

City

New Delhi

ZIP/Postal Code

110029

Country

India

Facility Name

Novartis Investigative Site

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

Novartis Investigative Site

City

Wilayah Persekutuan

ZIP/Postal Code

62502

Country

Malaysia

Facility Name

Novartis Investigative Site

City

México

State/Province

Distrito Federal

ZIP/Postal Code

14269

Country

Mexico

Facility Name

Novartis Investigative Site

City

Durango

ZIP/Postal Code

34270

Country

Mexico

Facility Name

Novartis Investigative Site

City

Rotterdam

ZIP/Postal Code

3015 GD

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Malaga

State/Province

Andalucia

ZIP/Postal Code

29010

Country

Spain

Facility Name

Novartis Investigative Site

City

Alzira

State/Province

Comunidad Valenciana

ZIP/Postal Code

46600

Country

Spain

Facility Name

Novartis Investigative Site

City

Istanbul

State/Province

TUR

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Novartis Investigative Site

City

Izmir

ZIP/Postal Code

35340

Country

Turkey

Facility Name

Novartis Investigative Site

City

Pendik / Istanbul

ZIP/Postal Code

34899

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

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Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

Cushings Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

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