An Open-Label Study to Assess the Safety and Efficacy of Levoketoconazole (COR-003) in the Treatment of Endogenous Cushing's Syndrome

Program: Abstracts - Orals, Poster Previews, and Posters
Session: FRI 354-376-Adrenal Tumors, Glucocorticoid Regulation and Action
Basic/Clinical
Friday, March 6, 2015: 1:00 PM-3:00 PM
Hall D-F, Adrenal (San Diego Convention Center)

Poster Board FRI-376
Roberto Salvatori, MD1, Anthony DelConte, MD2, Eliza B. Geer, MD3, Ted Koziol, PhD4 and Diane Jorkasky, MD5
1Johns Hopkins University, Baltimore, MD, 2Saint Joseph’s University, Philadelphia, PA, 3Icahn School of Medicine at Mount Sinai, New York City, NY, 4Cortendo AB, Radnor, PA, 5University of California San Francisco, San Francisco, CA
Endogenous Cushing´s syndrome (CS) is a rare but serious and potentially lethal disorder with an estimated incidence of 2-3 cases per million population persons per year and a prevalence of 30-60 cases per million. Incompletely controlled disease results in ≥5-fold increased mortality, mainly due to metabolic and cardiovascular complications. Racemic ketoconazole, an antifungal agent that at higher dosages reduces adrenal steroid production, is a commonly used off-label drug for the treatment of CS. Toxicity can be significant at higher doses, including liver damage. Cortendo AB is developing levoketoconazole, the single 2S,4R enantiomer of ketoconazole, as an investigational new drug for the treatment of cortisol hypersecretion. Levoketoconazole is purified from racemic ketoconazole and is hypothesized to provide better safety and efficacy than racemic ketoconazole. This study is currently enrolling patients and is the first clinical trial investigating the safety and efficacy of levoketoconazole in patients with endogenous CS. This is a single-arm, open-label, dose titration study to assess efficacy, safety, tolerability, and pharmacokinetics, and to identify the minimally effective and maximally tolerated doses of levoketoconazole in patients with CS. The primary study objective is to evaluate ascending doses of levoketoconazole, in order to identify the range of effective and safe doses that reduce mean 24-hour-urinary free cortisol (UFC) levels to less than or equal to the upper limit of normal (ULN) range of the assay at month 6 of the maintenance phase (with no prior dose increase). Patients aged ≥18 years with confirmed persistent or recurrent CS (with or without previous therapy) or newly diagnosed disease, if they are not candidates for surgery, will be included. After screening, the 3 treatment phases are: Dose Titration; Maintenance (6 months at therapeutic dose); and Extended Evaluation (6 months of continued treatment after Maintenance). Once the therapeutic dose is achieved (as confirmed by UFC), patients will enter the Maintenance phase and return monthly for 6 months for evaluation of efficacy (by UFC measurements), and clinical, safety, metabolic, quality of life, and pharmacokinetic assessments. During the Extended Evaluation phase, patients will return every 3 months and have interim laboratory evaluations. The proportion of responders at 6 months in the Maintenance phase will be estimated along with corresponding 95% confidence intervals (CIs). If the lower bound of the 95% CI is ≥20% in the intent-to-treat population, levoketoconazole will be considered an effective new medical therapy for the treatment of CS.

Disclosure: AD: Consultant, Cortendo AB. TK: Employee, Cortendo AB. DJ: Consultant, Cortendo AB. Nothing to Disclose: RS, EBG

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: Study funded by Cortendo AB. Dr Salvatori and Dr Geer are investigators in the trial sponsored by Cortendo AB. Dr DelConte and Dr Jorkasky are paid consultants to Cortendo AB. Dr Koziol is an employee of Cortendo AB. Connexion Healthcare provided writing and editorial assistance that was supported by funding from Cortendo AB.
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