Cushing's disease MedDRA version: 20.0 Level: SOC Classification code 10014698 Term: Endocrine disorders System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: Silycus
Product Code: [na]
Pharmaceutical Form:
CAS Number: 22888-70-6
Current Sponsor code: na
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 150-6
Sponsors
ISTITUTO BIOCHIMICO ITALIANO GIOVANNI LORENZINI S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Adult, i.e., age >= 18 years, female and male patients with active Cushing’s disease. Cushing’s disease will be diagnosed according to established guidelines. Patients will be either de novo diagnoses or persistent/recurrent disease Medical records will be collected and used to support the diagnosis 2- Mean value of 24-hour urinary free cortisol (UFC) in at least three collections 1.5 times above the upper limit of normal range (ULN) and elevated late night salivary cortisol (at least 2 measurements > ULN) or unsuppressed cortisol after 1 mg dexamethasone (i.e., serum cortisol at 8 AM >1.8 micrograms/deciliter) 3- Patients on inadequate or not tolerated medical treatments for Cushing’s disease amenable to minimum drug wash-out period 4- Patients with de novo Cushing’s disease if not surgical candidates or if surgery is delayed beyond the projected duration of the present study 5- Patients willing to provide written informed consent to participate in the study and adhere to protocol requirements 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1- Patients who do not fulfil criteria for active Cushing’s disease 2- Patients submitted to pituitary radiosurgery/radiotherapy within the past 3 years 3- Patients with de novo Cushing’s disease who are amenable to surgery which is available within the projected duration of the present study 4- Patients for whom the managing physician considers interruption of ongoing medical treatment for Cushing’s disease to be inappropriate 5- Pregnant and/or lactating women or women unwilling to use contraceptive medication and contraceptive devices for up to two months after silibinin withdrawal 6- Patients with active, severe kidney or liver disease 7- Patients with history of alcohol or drug abuse in the last 6 months 8- Patients with known hypersensitivity to components of Silycus® 9- Patients on mitotane will not be enrolled as a drug washout of at least 6 months is deemed unethical 10- Patients who are unwilling to perform study-related procedures 11- Any other criteria that may preclude patient participation according to investigator judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of Silycus® to decrease and/or normalize excess cortisol secretion in patients with active Cushing’s disease, assessed by either 24 hour urinary free cortisol, midnight salivary cortisol or suppression by low dose dexamethasone;Secondary Objective: - Evaluate the effect of Silycus® on signs and symptoms of hypercortisolism - Assess the safety and tolerability of Silycus® in patients with Cushing’s disease - Evaluate the PK profile of silibinin in patients with Cushing’s disease;Primary end point(s): Efficacy of silibinin will be assessed on UFC, late night salivary cortisol levels and suppression with low dose dexamethasone. The composite endpoint comprises: the number and percentage of patients in whom UFC normalized or decreased by at least 50% compared to pretreatment values, the number and percentage of patients with elevated late night salivary cortisol at baseline in whom salivary cortisol normalized and the number and percentage of patients who failed to suppress after low dose dexamethasone at baseline in whom normal suppression was restored. Efficacy will be assessed after 12 weeks of administration. UFC values will be averaged from three consecutive collections at both timepoints and salivary cortisol from 2 consecutive samples. We assume a primary efficacy response rate of 35%, thus if at least 5 patients fulfill the first primary endpoint, then Silycus® will be considered worthy of further research.;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Effect of silibinin on signs and symptoms of Cushing’s disease. Number and percentage of patients that experience changes in features of cortisol excess, as assessed by physical examination, case history, blood chemistry, will be calculated. In particular, the presence and severity of hypertension, excess weight, hirsutism in women (Ferriman-Gallwey score), facial plethora, reduced libido as well as Karnofsky performance status will be established. Further, changes in glucose control, electrolyte levels and white blood cell counts as well as any reduction in antihypertensive or glucose-lowering drugs will be quantified.;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment | — |
Countries
Italy
Contacts
Public ContactClinical Operations
Fullcro S.r.l.
Outcome results
None listed