Cushing’s disease MedDRA version: 14.1 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
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
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion 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
Exclusion criteria: Patients eligible for this study must not meet any of the following criteria: 1.Radiotherapy of the pituitary 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To document the safety of pasireotide s.c. in patients with CD;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;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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Czech Republic, Germany, Greece, Netherlands, Spain
Contacts
Public ContactMedizinischer Infoservice
Novartis Pharma GmbH
Outcome results
None listed