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

Cortendo

Status and phase: Completed; Phase 3

Conditions: Endogenous Cushing's Syndrome

Treatments: Drug: Placebo; Drug: Levoketoconazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT03277690

COR-2017-01

Details and patient eligibility

About

This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous Cushing's Syndrome (CS) previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.

Full description

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 Pharmacokinetics (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.

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 Urinary Free Cortisol (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups, including a placebo group

Levoketoconazole

Experimental group

Description:

Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo

Treatment:

Drug: Levoketoconazole

Placebo

Placebo Comparator group

Description:

Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole

Treatment:

Drug: Placebo