An open-label, multi-center, expanded access study of pasireotide s.c. in patients with Cushing’s disease (Seascape)

• Register: EUCTR
• Last refreshed on: 5 February 2018
• Main ID: EUCTR2010-024165-44-DE
• Date of registration: 12/05/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label, multi-center, expanded access study of pasireotide s.c. in patients with Cushing’s disease (Seascape)
• Scientific title: An open-label, multi-center, expanded access study of pasireotide s.c. in patients with Cushing’s disease (Seascape) - Seascape
• Date of first enrolment: 05/08/2011
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024165-44
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Germany, Greece, Netherlands, Spain

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to meet all of the following 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 2-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.
(* if IPSS had previously been performed without CRH (e.g.with DDAVP), then a central to peripheral pre-stimulation gradient > 2 is required. If IPSS had not previously been performed, IPSS with CRH stimulation is required)
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 this 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): 1 week
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients eligible for this study must not meet any of the following 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) known to increase the QT interval
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 3 months 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 investig

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Cushing’s disease
MedDRA version: 14.1 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Trade Name: Signifor
Product Name: Signifor
Product Code: SOM230 300µg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pasireotide
Current Sponsor code: SOM230B
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 300-

Trade Name: Signifor
Product Name: Signifor
Product Code: SOM230 600µg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pasireotide
Current Sponsor code: SOM230B
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 600-

Trade Name: Signifor
Product Name: Signifor
Product Code: SOM230 900µg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pasireotide
Current Sponsor code: SOM230B
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 900-

Primary Outcome(s)

Primary end point(s): The proportion of patients having a drug-related adverse event that is recorded as grade 3 or 4 or as a serious adverse event.

Secondary Objective: -the efficacy of pasireotide s.c. in normalizing mean 24h-UFC at Week
12, 24 and 48, separately
- the efficacy of pasireotide s.c. in achieving at least 50% reduction of
mean 24h-UFC from baseline at Week 12, 24 and 48, separately
- the changes in clinical signs and symptoms
- the changes in patient-reported outcome questionnaires (CushingQoL
and WPAI-GH)
- the effects of pasireotide s.c. on the GH/IGF-I axis
- the overall safety and tolerability of pasireotide s.c. in patients with CD

Main Objective: To document the safety of pasireotide s.c. in patients with CD

Secondary Outcome(s)

Secondary end point(s): The secondary end points are:
•proportion of patients with mean 24h-UFC = ULN at Week 12, 24 and
48, separately
•proportion of patients achieving a reduction of mean 24h-UFC = 50%
from baseline at Week 12, 24 and 48, separately
•change from baseline to Week 12, 24 and 48 in clinical signs and
symptoms
•change from baseline to Week 12, 24 and 48 in CushingQoL and WPAIGH
scores
•change from baseline to Week 12, 24 and 48 in GH and IGF-I separately
•incidence of AEs, and laboratory, vital signs and electrocardiographic
abnormalities.
•changes in laboratory values, electrocardiograms readings, and in vital
signs values

Secondary ID(s)

CSOM230B2406

Source(s) of Monetary Support

Novartis Pharma Services AG