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

Phase 3

Completed

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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.	max. 9.5 weeks	Urinary free cortisol (UFC) level measurement: Loss of therapeutic response is inferred based on mUFC from three 24-hour UFC measurements obtained at any visit from second through final Randomized Withdrawal Phase visits (RW1 through RW5 inclusive) when: (1) mUFC is above 1.5X the ULN of the central laboratory's reference range, OR (2) mUFC is more than 40% above the baseline (RW0) value, if the RW0 value is above the ULN (i.e. \>1.0X ULN)1, OR (3) an early rescue criterion is met.

Secondary Outcome Measures

Name	Time	Method

Locations (45): Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital
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Los Angeles, California, United States
Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center
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Los Angeles, California, United States
UCLA School of Medicine, Medicine/Endocrinology Department
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Los Angeles, California, United States
The Center for Diabetes and Endocrine Care
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Fort Lauderdale, Florida, United States
Emory University, Neurosurgery
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Atlanta, Georgia, United States
Northwestern University, Medicine - Endocrinology
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Chicago, Illinois, United States
Johns Hopkins University, Endocrinology Department
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Baltimore, Maryland, United States
University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND
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Ann Arbor, Michigan, United States
Washington University School of Medicine, Endocrinology
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Saint Louis, Missouri, United States
Columbia University, College of P&S Medicine/Neuro-endocrine Unit
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New York, New York, United States
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Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital
🇺🇸Los Angeles, California, United States