SILIBININ for Cushing's disease

Inclusion criteria

• {"criterion_text":"- 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.\n- 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)\n- Patients on inadequate or not tolerated medical treatments for Cushing’s disease amenable to minimum drug wash-out period\n- Patients with de novo Cushing’s disease if not surgical candidates or if surgery is delayed beyond the projected duration of the present study\n- Patients willing to provide written informed consent to participate in the study and adhere to protocol requirements"}

Exclusion criteria

• {"criterion_text":"- Patients who do not fulfil criteria for active Cushing’s disease\n- Patients who are unwilling to perform study-related procedures\n- Any other criteria that may preclude patient participation according to investigator judgement.\n- Patients submitted to pituitary radiosurgery/radiotherapy within the past 3 years\n- Patients with de novo Cushing’s disease who are amenable to surgery which is available within the projected duration of the present study\n- Patients for whom the managing physician considers interruption of ongoing medical treatment for Cushing’s disease to be inappropriate\n- Pregnant and/or lactating women or women unwilling to use contraceptive medication and contraceptive devices starting from one month before Silycus® administration and for up to two months after silibinin withdrawal\n- Patients with active, severe kidney or liver disease\n- Patients with history of alcohol or drug abuse in the last 6 months\n- Patients with known hypersensitivity to components of Silycus®\n- Patients on mitotane will not be enrolled as a drug washout of at least 6 months is deemed unethical"}

Primary endpoints

• {"endpoint_text":"- Efficacy of silibinin will be assessed on UFC, late night salivary cortisol levels and suppression with low dose dexamethasone.","definition_or_measurement_approach":"Assessment by 24-hour urinary free cortisol (UFC), late night (midnight) salivary cortisol measurements and suppression after low dose dexamethasone as specified in main objective."}
• {"endpoint_text":"- The composite endpoint comprises: the percentage of patients in whom UFC normalized or decreased by at least 50% compared to pretreatment values, the percentage of patients with elevated late night salivary cortisol at baseline in whom salivary cortisol normalized 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.","definition_or_measurement_approach":"Composite of: % patients with UFC normalization or ≥50% reduction vs pretreatment, % patients with normalization of late night salivary cortisol, % patients with restoration of normal suppression after low dose dexamethasone; assessed at 12 weeks of administration."}

Secondary endpoints

• {"endpoint_text":"- Establish the effect of Silycus® on clinical signs and symptoms of Cushing’s disease. These effects, i.e. changes in body weight, blood pressure, glucose control, electrolyte derangements, leukocytosis, will be assessed after 12 weeks administration","definition_or_measurement_approach":"Changes in clinical signs and symptoms including body weight, blood pressure, glucose control, electrolyte derangements, leukocytosis assessed at 12 weeks."}
• {"endpoint_text":"- Analysis of safety of Silycus® administration based on frequency and severity of adverse events","definition_or_measurement_approach":"Safety assessed by recording frequency and severity of adverse events."}
• {"endpoint_text":"- Evaluation of the PK profile of silibinin in patients with Cushing’s disease (after the first dose, uptitration and at steady state)","definition_or_measurement_approach":"PK sampling to characterise silibinin profile after first dose, during uptitration and at steady state."}

Italy

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

396

Number Of Sites

5

Number Of Participants

15

Primary sponsor

Full Name

Istituto Biochimico Italiano Giovanni Lorenzini S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Fullcro S.r.l.","duties_or_roles":"codes: 1,10,11,12,14,5,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Pharmaron UK Limited","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Gem Forlab S.r.l.","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Istituto Auxologico Italiano","duties_or_roles":"ECG reader (code: 15)","organisation_type":"Hospital/Clinic/Other health care facility"}