A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.

• Register: ClinicalTrials.gov
• Last refreshed on: 22 March 2021
• Main ID: NCT03277690
• Date of registration: 07/09/2017
• Prospective Registration: Yes
• Primary sponsor: Cortendo AB
• Public title: A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.
• Scientific title: A Double-blind, Placebo-Controlled, Randomized Withdrawal Following Open Label Therapy Study to Assess the Safety and Efficacy of Levoketoconazole (2S, 4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome
• Date of first enrolment: September 26, 2017
• Target sample size: 44
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03277690
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Bulgaria, Denmark, France, Greece, Hungary, Israel, Italy, Netherlands, Poland, Romania, Spain, United States

Contacts

• Name: Xavier Valencia, MD
• Affiliation: Cortendo AB

Key inclusion & exclusion criteria

INCLUSION CRITERIA:

SONICS STUDY COMPLETERS:

Completed the final SONICS visit (M12) and have demonstrated maintenance of clinical
response on a stable Therapeutic Dose of levoketoconazole for at least 12 weeks prior to
study entry.

ALL OTHERS:

- Confirmed newly diagnosed, persistent or recurrent endogenous Cushing's syndrome of
any etiology, except secondary to malignancy (including pituitary or adrenal
carcinoma).

- Elevated mean 24-hour UFC levels at least 1.5X upper limit of the normative range of
the study's central laboratory assay and from a minimum of three measurements from
adequately collected urine.

- Presence of abnormal values from at least one of these two diagnostic tests:

- Abnormal Dexamethasone Suppression Test (DST) OR

- Elevated late night salivary cortisol concentrations (at least two measurements)
each greater than the upper limit of the study's central laboratory normative
range

- Non-candidates for CS-specific surgery, refuse surgery or surgery will be delayed
until after study completion and agree to complete this study prior to surgery.

- If post-surgical for CS-specific surgery, then no significant post-operative sequelae
remain and the risk of such sequelae is considered negligible.

EXCLUSION CRITERIA:

Subjects will be excluded from the study if ANY of the following criteria are met (NOTE:
exclusion criteria apply to and must be assessed in both cohorts):

- Enrolled in SONICS but have not completed SONICS through Visit M12.

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

- Cyclic Cushing's syndrome with multi-week periods of apparent spontaneous CS
remission.

- Non-endogenous source of hypercortisolism, including pharmacological corticosteroids
or ACTH.

- Radiotherapy of any modality directed against the source of hypercortisolism within
the last 5 years.

- Treatment with mitotane within 6 months of enrollment.

- History of malignancy, including adrenal or pituitary carcinomas (other than low-risk,
well-differentiated carcinomas of thyroid, breast or prostate that are very unlikely
to require further treatment in the opinion of the treating physician, or squamous
cell or basal cell carcinoma of the skin).

- Clinical or radiological signs of compression of the optic chiasm.



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

Health Condition(s) or Problem(s) studied

Endogenous Cushing's Syndrome

Intervention(s)

Drug: Placebo

Drug: Levoketoconazole

Primary Outcome(s)

Number of subjects with loss of therapeutic response to levoketoconazole upon withdrawing to placebo compared with the proportion of subjects with loss of therapeutic response upon continuing treatment with levoketoconazole. [Time Frame: max. 9.5 weeks]

Secondary ID(s)

COR-2017-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors