Treatment for Endogenous Cushing's Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 29 March 2021
• Main ID: NCT01838551
• Date of registration: 19/04/2013
• Prospective Registration: Yes
• Primary sponsor: Cortendo AB
• Public title: Treatment for Endogenous Cushing's Syndrome SONICS
• Scientific title: An Open Label Study to Assess the Safety and Efficacy of COR-003 (Levoketoconazole) in the Treatment of Endogenous Cushing's Syndrome
• Date of first enrolment: August 2014
• Target sample size: 90
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01838551
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Bulgaria, Canada, Czech Republic, Czechia, Denmark, France, Georgia, Germany, Hungary, Israel, Italy, Netherlands, Poland, Serbia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Fredric J Cohen, MD
• Affiliation: Cortendo AB

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. Male or female =18 years of age

2. Able to provide written informed consent prior to any study procedures being
performed; eligible subjects must be able to understand the informed consent form
prior to inclusion into the study.

3. Confirmed diagnosis of newly diagnosed, persistent or recurrent Cushing's disease (CD)
or endogenous CS of other etiology if subjects are not candidates for surgery or
radiotherapy within the 18 months after enrollment.

Previous medical records will be collected and used to support the diagnosis of CD or
endogenous CS of other etiology, including the following etiologies:

- Ectopic adrenocorticotropic hormone (ACTH) secretion, i.e. ACTH not of pituitary
origin

- Ectopic corticotropin-releasing hormone (CRH) secretion

- Adrenal-dependent CS (i.e. adrenal adenoma (NOT carcinoma), adrenal hyperplasia,
etc.)

- Etiology unknown.

4. Must have elevated mean 24 hour UFC levels =1.5X ULN based on the normative range of
the central lab assay and on a minimum of four measurements from adequately collected
urine.

5. In addition to elevated mean UFC, presence of abnormal values from one of the
following tests:

- Abnormal DST: Elevated 8 AM serum cortisol =1.8 micrograms/dL (50 nmol/L) after 1
mg dexamethasone orally at 11 PM the evening prior (if not conducted already in
the diagnostic workup of the subject within the previous 2 months before start of
Screening Phase; in that case previous test results and details of conduct will
need to be available by the Baseline Visit)

- Elevated late night salivary cortisol concentrations (at least two measurements)
>ULN

6. Previously irradiated subjects with CD or endogenous CS of other etiology will be
allowed as long as the radiation treatment occurred > 4 years ago and subjects have
not exhibited evidence for improvement in their underlying CD for 6 months prior to
the Screening visit. The total number of previously irradiated subjects enrolled in
this study will not exceed 10.

7. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse
surgery, or in whom surgery will be delayed for at least 18 months following
enrollment. Subjects may be allowed to participate in the trial while awaiting
surgery, but must agree to complete this study prior to surgery.

8. Subjects on treatment for CD or endogenous CS of other etiology for whom treatment has
been inadequate or not well tolerated must agree to minimum washout periods prior to
the Baseline Visit as specified.

Key Exclusion Criteria

1. Subjects with Pseudo-Cushing's syndrome based on assessment of the Investigator.

2. Subjects with cyclic CS based on assessment of the Investigator

3. Subjects with a non-endogenous source of hypercortisolism such as exogenous source of
glucocorticoids or therapeutic use of ACTH.

4. Known inherited syndrome as the cause of hypercortisolism, including but not limited
to multiple endocrine neoplasia Type 1, McCune Albright Syndrome and Carney Complex

5. Subjects with adrenal carcinoma

6. History of malignancy, other than thyroid, early stage prostate, squamous cell and
basal cell carcinoma, within 3 years prior to the Screening Phase.

7. Subjects with QTc interval of >470 msec during the Screening Phase.

8. Pre-existing hepatic disease; subjects with mild to moderate hepatic steatosis
consistent with fatty infiltration (non-alcoholic fatty liver disease [NAFLD] are
allowed).

9. History of documented or suspected drug-induced liver injury requiring drug
discontinuation of ketoconazole or any azole antifungals.

10. Subjects who receive any prohibited concomitant medication and cannot discontinue it
safely prior to the Baseline Visit.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Endogenous Cushing's Syndrome

Intervention(s)

Drug: Levoketoconazole

Primary Outcome(s)

Reduction in urinary free cortisol in patients with endogenous Cushing's Syndrome. [Time Frame: 6 months of maintenance phase therapy without a prior dose increase during that phase]

Secondary ID(s)

COR-2012-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors