Extension of a clinical trial to assess the safety of a study drug called "CORT125134" in the treatment of Cushing Syndrome

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2018-001616-30-HU
• Date of registration: 14/05/2018
• Prospective Registration: Yes
• Primary sponsor: Corcept Therapeutics Incorporated
• Public title: Extension of a clinical trial to assess the safety of a study drug called "CORT125134" in the treatment of Cushing Syndrome
• Scientific title: An Open-Label Extension Study of the Safety of Relacorilant (CORT125134) in the Treatment of the Signs and Symptoms of Endogenous Cushing Syndrome
• Date of first enrolment: 09/07/2018
• Target sample size: 75
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001616-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Hungary, Italy, United States

Contacts

• Name: Clinical Operations
• Affiliation: Corcept Therapeutics Incorporated

• Name: Clinical Operations
• Affiliation: Corcept Therapeutics Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
All Patients
1. Have completed a Corcept-sponsored study of relacorilant in endogenous Cushing syndrome through the treatment period with at least 80% adherence with scheduled dosing and visits.
2. According to Investigator’s opinion will benefit from continuing treatment with relacorilant.
3. Provide written informed consent.
4. If a female of childbearing potential, patients must be willing to use a highly effective method of contraception from 30 days before study entry until 30 days after the last dose of study drug. Male patients with a female partner must agree to 2 forms of contraception, one of which must be a double-barrier method, from study entry until 30 days after the last dose of study drug. Highly effective methods of contraception include abstinence, oral contraceptives combined with a barrier method, diaphragm with vaginal spermicide, intrauterine device, male condom and partner using vaginal spermicide, and surgical sterilization (=6 months postsurgery).
5. Are willing to continue to refrain from using drugs that inhibit steroid biosynthesis by the adrenal cortex or ACTH secretion by a pituitary or extrapituitary ACTH secreting tumor. Mitotane is acceptable in patients with adrenal carcinoma.
6. Are able to return to the investigative site to complete the study evaluations outlined in the protocol.
7. For patients with Cushing syndrome due to an ACTH-secreting pituitary tumor, are able to obtain pituitary MRI imaging (obtained up to 3 months before to 6 weeks after start of treatment in this study) to assess changes in tumor size during dosing.

Patients Who Enter Study >8 Weeks After Completing the Parent Study
8. Have a diagnosis of endogenous Cushing syndrome confirmed by 2 of the 3 following biochemical test criteria:
• Urinary free cortisol above the upper limit of normal (ULN) (50.0 µg/24 h) in at least 2 complete 24-hour collections within 3 weeks before Day 1.
• Late-night salivary cortisol above the ULN in at least 2 collections using a salivette within 3 weeks before Day 1.
• Results from the dexamethasone suppression test performed during the parent study.
Patients requiring washout of a medication for Cushing syndrome must complete the screening 24-hour UFC tests and salivary cortisol tests after a minimum washout of 2 weeks for adrenostatic medications and short-acting somatostatin analogs, 4 weeks for mifepristone and dopamine agonists, and 6 weeks for long-acting somatostatin ligands and within 3 weeks before Day 1 dosing.

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 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion criteria:
1. Have been prematurely discontinued from relacorilant study treatment in the parent study for any reason
2. Are planning to start another Cushing syndrome drug after starting participation in this extension study.
3. Have an acute or unstable medical problem that could be aggravated by relacorilant treatment.
4. Are taking the following medications from the times specified below before the Study CORT125134-452 Day 1 visit and/or through the entire study period:
• Medications used in the treatment of Cushing syndrome, with the exception of relacorilant, are prohibited:
– Adrenostatic medications: metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate 2 weeks before Day 1 through the end of this study
– Neuromodulator drugs that act at the hypothalamic-pituitary level: serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), gamma-aminobutyric acid agonists (sodium valproate), and somatostatin receptor ligands (octreotide long-acting release [LAR], pasireotide LAR, lanreotide) from 8 weeks before Day 1 through the end of this study. Use of short-acting somatostatin analogs (octreotide, pasireotide) from 4 weeks before Day 1 through the end of this study.
• Mifepristone, from 4 weeks before Day 1 through the end of this study.
• Strong CYP3A4 inhibitors (including grapefruit, grapefruit juice, or grapefruit-containing products) during treatment with relacorilant.
5. Plan to use systemic, potent (Group III), and potent intra-articular corticosteroids from Day 1 through the end of the study.
6. Have received investigational treatment (drug, biological agent, or device) other than relacorilant within 4 weeks of study entry.
7. Have a history of an allergic reaction or intolerance to relacorilant.
8. Have uncorrected hypokalemia (potassium level of < 3.5 mEq/L) within 2 weeks before enrollment in this study (Day 1).
9. Have uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
10. Have renal failure as defined by a serum creatinine of =2.2 mg/dL.
11. Have elevated total bilirubin >1.5 × the ULN or elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =3 × ULN.
12. Have a clinically significant ECG abnormality at baseline, which, in the opinion of the Investigator, will make the patient an unsuitable candidate for the study.
13. Have a confirmed baseline QT interval corrected using Fridericia’s formula (QTcF) >450 ms for males and >470 ms for females in the presence of a normal QRS interval (QRS <120 ms) or a history of additional risk factors for torsades de pointes.
14. Women of childbearing potential: are pregnant based on serum pregnancy test.
15. Have an ongoing SAE that started in the parent study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Endogenous Cushing Syndrome
MedDRA version: 20.0 Level: LLT Classification code 10011657 Term: Cushings syndrome System Organ Class: 100000004860

Therapeutic area: Body processes [G] - Physiological processes [G07]

Intervention(s)

Product Code: CORT125134
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Relacorilant
CAS Number: 1496510-51-0
Current Sponsor code: CORT125134
Other descriptive name: (R)-(1-(4-FLUOROPHENYL)-6-((1-METHYL-1H-PYRAZOL-4-YL)SULFONYL)-4,4A,5,6,7,8-HEXAHYDRO-1H-PYRAZOLO[3,4-G]ISOQUINOLIN-4A-YL)(4-(TRIFLUOROMETHYL)PYRIDIN-2-YL)METHANONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): • Incidence of TEAEs
• Changes from baseline levels in clinical laboratory measurements
• Changes from baseline in physical examinations and vital sign measurements
• Changes from baseline in ECG variables
• Changes from baseline in pituitary tumors based on MRI scans in patients with Cushing disease.
• PK measurements

Main Objective: To assess the long-term safety of relacorilant in the treatment of the signs and symptoms of endogenous Cushing syndrome

Secondary Objective: To assess the long-term benefit of relacorilant in the treatment of signs and symptoms of endogenous Cushing syndrome

Timepoint(s) of evaluation of this end point: Monthly :
- Incidence of TEAEs

Every 3 and 12 Months and at End of Study:
- Adverse event monitoring
- Clinical laboratory measurements
- Physical examination
- Vital signs including BP, heart rate, respiratory rate, and oral body temperature
- 12-Lead ECG
- PK sampling

Every 12 Months and at End of Study:
- Pituitary MRI scan

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 3 and 12 Months and at End of Study:
- HbA1c
- ABPM
- Physician’s Global Assessment
- Weight and waist circumference
- CushingQoL Questionnaire
- Biochemical markers of bone remodeling
- HPA axis parameters
- Late-night salivary cortisol
- Lipid panel (fasting)
- Sex hormone levels
- Menstrual cycle information

- Thyroid function tests

Secondary end point(s): Changes from baseline in the following:
- HbA1c and insulin resistance indices in patients with Diabetes mellitus or glucose intolerance if an oral glucose tolerance test (OGTT) was a key efficacy assessment in the parent study
– BP by ambulatory BP measurements (ABPM) in patients with uncontrolled hypertension (HTN) if this was a key efficacy assessment in the parent study and in patients with controlled HTN taking at least one anti-HTN medication
– Physician’s Global Assessment of Disease Severity
– Weight and waist circumference
– Quality-of-life (CushingQoL) questionnaire
– Biochemical markers of bone remodeling
– HPA axis markers
– Cortisol concentration in blood, urine, and saliva
– Lipid levels
– Sex steroid hormone and gonadotropin levels
– Menstrual cycle characterization (premenopausal women not taking hormonal contraceptive medication)
– Thyroid function tests

Secondary ID(s)

CORT125134-452

Source(s) of Monetary Support

Corcept Therapeutics Incorporated