A Double-Blind, Placebo-Controlled, Crossover Pilot Study of the Efficacy and Safety of Fluasterone Buccal Tablet in the Control of Hyperglycemia in Adults with Endogenous Cushing’s Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sterotherapeutics LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

2 May 2025 → ongoing

Decision date (initial)

2024-03-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sterotherapeutics, LLC.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the effect of buccal fluasterone on hyperglycemia associated with the diagnosis of endogenous hypercortisolemia (possible Cushing’s syndrome) in patients suffering from impaired glucose tolerance or diabetes mellitus

Secondary objectives 4

1. To determine the safety and tolerability of buccal fluasterone when administered daily for 12 weeks
2. To evaluate the potential effect of buccal fluasterone on lipid profile in subjects with Cushing’s Syndrome
3. To evaluate the potential effect of buccal fluasterone on body habitus in subjects with Cushing’s syndrome
4. To evaluate the potential effect of buccal fluasterone in subjects with Cushing’s Syndrome who have evidence of nonalcoholic fatty liver disease.

Conditions and MedDRA coding

Cushing Syndrome

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female patients aged 18 to 75 years, inclusive
2. Patient has read and signed the IRB/ Institutional Ethics Committee (IEC) approved ICF before screening procedures are undertaken
3. 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
4. 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
5. 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.
6. 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 25

1. Has an acute or unstable medical condition
2. 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
3. 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
4. Is a female who is breast feeding
5. 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
6. Has received pituitary radiation (stereotactic radiosurgery) within 2 years of Screening Visit #1 or conventional radiation within 3 years of Screening Visit #1
7. Has a history of an allergic reaction to fluasterone or DHEA
8. 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
9. Has non-neoplastic hypercortisolism
10. Has history of currently active malignancy involving any organ system (other than localized basal cell carcinoma of the skin and adrenal carcinoma)
11. 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
12. 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
13. Has a history of alcohol or drug abuse within 6 months prior to Screening Visit #1
14. 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 %)
15. Has HbA1c >9% within the last 3 months
16. Has uncontrolled hypertension defined as >170/110 mmHg
17. Has uncontrolled hypothyroidism or hyperthyroidism
18. Has received treatment with mifepristone within the 2 months period prior to Screening Visit #1
19. Is receiving other medicinal products interfering with cortisol production and/or metabolism
20. 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
21. 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)
22. Has hypokalemia (serum potassium < 3.0 mg/dL) at Screening Visit #1
23. Has positive urine drug screen for drugs of abuse, excepting prescribed medications
24. Is a patient who, in the opinion of the Investigator, is not able to comply with study requirements
25. Has G6PD deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. The change in AUCglucose based on the 2-hour oGTT at week 6 versus baseline during each of the 12-week treatment periods.
2. The change in HbA1c at weeks 6 and 12 versus baseline during each of the 12-week treatment periods
3. The change in serum lipid profiles at weeks 6 and 12 versus baseline during each of the 12-week treatment periods
4. 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
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sterotherapeutics LLC

Sponsor organisation

Sterotherapeutics LLC

Address

3805 Old Easton Road

City

Doylestown

Postcode

18902-8400

Country

United States

Scientific contact point

Organisation

Sterotherapeutics LLC

Contact name

Medical Director

Public contact point

Organisation

Sterotherapeutics LLC

Contact name

Medical Director

Third parties 2

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications