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

Stopped early · Phase 2

Conditions studied: Cushings Disease

In brief

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.

Key facts

Study ID

NCT01915303

Run by

Novartis Pharmaceuticals

People needed

68

Starts

2014-03-06

Expected to finish

2019-09-04

Last updated by the study team

2020-09-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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

Where it is running

• University of Alabama at Birmingham The Kirklin Clinic — Birmingham, Alabama, United States
• Oregon Health and Science University SOM230B2411 — Portland, Oregon, United States
• Novartis Investigative Site — Caba, Buenos Aires, Argentina
• Novartis Investigative Site — Ghent, Belgium
• Novartis Investigative Site — Leuven, Belgium
• Novartis Investigative Site — Curitiba, Paraná, Brazil
• Novartis Investigative Site — Rio de Janeiro, Rio de Janeiro, Brazil
• Novartis Investigative Site — Porto Alegre, Rio Grande do Sul, Brazil
• Novartis Investigative Site — São Paulo, São Paulo, Brazil
• Novartis Investigative Site — Bogota, Cundinamarca, Colombia
• Novartis Investigative Site — Vandœuvre-lès-Nancy, France
• Novartis Investigative Site — Erlangen, Germany
• Novartis Investigative Site — Athens, Greece
• Novartis Investigative Site — Thessaloniki, Greece
• Novartis Investigative Site — Budapest, Hungary
• Novartis Investigative Site — Budapest, Hungary
• Novartis Investigative Site — Vellore, Tamil Nadu, India
• Novartis Investigative Site — Chandigarh, India
• Novartis Investigative Site — New Delhi, India
• Novartis Investigative Site — Naples, Italy
• Novartis Investigative Site — Wilayah Persekutuan, Malaysia
• Novartis Investigative Site — Mexico City, Mexico City, Mexico
• Novartis Investigative Site — Durango, Mexico
• Novartis Investigative Site — Rotterdam, Netherlands
• Novartis Investigative Site — Málaga, Andalusia, Spain

Full record on ClinicalTrials.gov

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