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

This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration
study in subjects with endogenous CS that will assess efficacy, safety, tolerability, and PK
of levoketoconazole. There are two populations (cohorts) of subjects: (1) subjects which were
previous levoketoconazole study completers and (2) subjects that are levoketoconazole
treatment naïve subjects.

Study methodology varies by cohort prior to randomization only. Following initial screening
(washout as needed) and Dose Titration and Maintenance Periods, as applicable, this study
will be conducted in two double-blind phases (a Withdrawal Phase and a Restoration Phase).
The levoketoconazole-naïve cohort will need to go through the Dose Titration and Maintenance
Phase. The longest anticipated total study participation duration is approximately 51 weeks.

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.