FLUASTERONE for Cushing's syndrome

Inclusion criteria

• {"criterion_text":"- Male or female patients aged 18 to 75 years, inclusive\n- Patient has read and signed the IRB/ Institutional Ethics Committee (IEC) approved ICF before screening procedures are undertaken\n- Has been evaluated within the previous 12 months for the possibility of endogenous Cushing syndrome (caused by either ACTH-dependent or ACTH-independent etiologies), meaning to fulfil 2 out of the 3 following criteria as per European guidelines:  an elevated 24-hour urine free cortisol (UFC), above the upper limit of normal (ULN) as per the reference range of the laboratory assay, on two occasions, or  an abnormal response to an overnight 1-mg dexamethasone suppression test (DST), i.e., an elevated blood cortisol over 1.8 µg/dL (50 nmol/L) measured between 8 AM and 9 AM, after a 1-mg dexamethasone oral administration between 11 PM and 12 PM the previous night,  or an abnormal midnight serum or salivary cortisol levels prior to initiation of study treatment, meaning:  for “sleeping” midnight serum cortisol to be greater than 1.8 μg/dl (>50 nmol/liter), OR for “awake” midnight serum cortisol to be greater than 7.5 μg/dl (>207 nmol/liter), or  for late-night salivary cortisol (LNSC) to be above the ULN as per the reference range of the laboratory assay\n- Has been diagnosed with impaired glucose tolerance (IGT), i.e., 2-hour plasma glucose ≥140 mg/dl and <200 mg/dl during an oGTT, or type 2 diabetes mellitus according to EASD/ADA guidelines, with HbA1c <9% during the last three months\n- If the patient receives treatment(s) for hyperglycemia, the dose(s) must have been stable for the 60 days prior to the Pre-Screening Visit.\n- If the patient has received post-operative glucocorticoid replacement therapy following surgery for Cushing’s Disease, he/ she must have discontinued such therapy for at least one week, or 5 half-lives, whichever is longer, prior to Screening Visit #1."}

Exclusion criteria

• {"criterion_text":"- Has an acute or unstable medical condition\n- Has history of currently active malignancy involving any organ system (other than localized basal cell carcinoma of the skin and adrenal carcinoma)\n- Has electrocardiogram (ECG) at Screening Visit #1 that shows prolongation of QTcF interval >450 msec in males or >470 msec in females, or any clinically significant dysrhythmia\n- Has a history of congestive heart failure, unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, or acute myocardial infarction within 12 months of Screening Visit #1\n- Has a history of alcohol or drug abuse within 6 months prior to Screening Visit #1\n- Has 2-hour plasma glucose <140 mg/dl in oGTT at Screening Visit #1, unless under stable treatment for hyperglycemia for at least 2 months prior to Screening visit #1 (lowest acceptable 2-hour plasma glucose in oGTT at Screening visit #1 is 110 mg/dL and HbA1c is 6.0 %)\n- Has HbA1c >9% within the last 3 months\n- Has uncontrolled hypertension defined as >170/110 mmHg\n- Has uncontrolled hypothyroidism or hyperthyroidism\n- Has received treatment with mifepristone within the 2 months period prior to Screening Visit #1\n- Is receiving other medicinal products interfering with cortisol production and/or metabolism\n- Is a pregnant woman or woman of childbearing potential (WOCBP) who is receiving oral contraceptive pills or is unable or unwilling to utilize appropriate methods of contraception during the study\n- Has clinical laboratory results for hematology at Screening Visit #1 that includes one or more of the following: hemoglobin <9 g/dL, total WBC <3000 cells/mm3, ANC <1500 cells/mm3, platelet count <100K /mm3\n- Has clinical laboratory results for chemistry at Screening Visit #1 that includes one or more of the following: ALT >5 x ULN, AST >5 x ULN, bilirubin >2 x ULN, estimated creatinine clearance <50 mL/min (by Cockroft-Gault equation)\n- Has hypokalemia (serum potassium < 3.0 mg/dL) at Screening Visit #1\n- Has positive urine drug screen for drugs of abuse, excepting prescribed medications\n- Is a patient who, in the opinion of the Investigator, is not able to comply with study requirements\n- Has G6PD deficiency\n- Is a male subject with female partner of childbearing potential, who is unwilling to use a condom and his partner to use an additional form of adequate contraception\n- Is a female who is breast feeding\n- Has received treatment with an investigational product (drug, biologic agent, and/or device) within 30 days or 5 half-lives, whichever is longer at the time of Screening Visit #1\n- Has received pituitary radiation (stereotactic radiosurgery) within 2 years of Screening Visit #1 or conventional radiation within 3 years of Screening Visit #1\n- Has a history of an allergic reaction to fluasterone or DHEA\n- Has a non-endogenous source of hypercortisolism such as factitious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing’s syndrome), factitious or therapeutic use of ACTH\n- Has non-neoplastic hypercortisolism"}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is the change in area under the curve for glucose (AUCglucose) based on the 2-hour oGTT at week 12 versus baseline during each of the 12-week treatment periods.","definition_or_measurement_approach":"AUCglucose calculated from the 2-hour oral glucose tolerance test (oGTT) at week 12 compared to baseline during each 12-week treatment period."}

Secondary endpoints

• {"endpoint_text":"- The change in AUCglucose based on the 2-hour oGTT at week 6 versus baseline during each of the 12-week treatment periods.","definition_or_measurement_approach":"AUCglucose from 2-hour oGTT at week 6 versus baseline during each 12-week treatment period."}
• {"endpoint_text":"- The change in HbA1c at weeks 6 and 12 versus baseline during each of the 12-week treatment periods","definition_or_measurement_approach":"Change in measured HbA1c at weeks 6 and 12 versus baseline during each 12-week treatment period."}
• {"endpoint_text":"- The change in serum lipid profiles at weeks 6 and 12 versus baseline during each of the 12-week treatment periods","definition_or_measurement_approach":"Measured serum lipid profile parameters at weeks 6 and 12 versus baseline during each 12-week treatment period."}
• {"endpoint_text":"- The change in body habitus as evaluated by DEXA scanning at weeks 6 and 12 versus baseline during each of the 12-week treatment periods","definition_or_measurement_approach":"Body composition assessed by DEXA at weeks 6 and 12 versus baseline during each 12-week treatment period."}
• {"endpoint_text":"- The change in hepatic steatosis/fibrosis as evaluated by TEand MRI-PDFF at week 12 versus baseline during each of the 12-week treatment periods.","definition_or_measurement_approach":"Hepatic steatosis/fibrosis assessed by transient elastography (TE) and MRI-PDFF at week 12 versus baseline during each 12-week treatment period."}

Greece

Earliest CTIS Part Ii Submission Date

07-12-2023

Latest Decision Or Authorization Date

08-04-2026

Processing Time Days

853

Number Of Sites

9

Number Of Participants

24

Primary sponsor

Full Name

Sterotherapeutics LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pharmassist Ltd.

Responsibilities

sponsorDuties codes: 1, 11, 12, 13, 2, 8 (roles as listed in CTIS thirdParty entry)

Third parties

• {"country":"Greece","full_name":"Biomedical Research Foundation Of The Academy Of Athens","duties_or_roles":"PK Samples Analysis; sponsorDuties codes present: 15 and 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"Pharmassist Ltd.","duties_or_roles":"sponsorDuties codes present: 1, 11, 12, 13, 2, 8","organisation_type":"Pharmaceutical company"}