Levoketoconazole: An Investigational Adrenal Steroidogenesis Inhibitor for Endogenous Cushing’s Syndrome

Received orphan drug designation from the FDA and the European Medicines Agency

Learn about endogenous Cushing's syndrome

Pituitary World News (PWN), a not-for-profit news and patient advocacy organization that seeks to raise awareness of pituitary disease and related illnesses, conducted an in-depth interview with Maria Fleseriu, MD, FACE, professor of Medicine and Neurological Surgery and director of the Oregon Health Sciences University Pituitary Center and principal investigator of the SONICS and LOGICS studies.

The discussion addresses a range of Cushing’s syndrome topics, including the latest advances in medical treatments, new therapies on the horizon, key results from both the LOGICS and SONICS phase 3 studies of levoketoconazole, and the associated challenges and unmet needs in the diagnosis and treatment of the disease.

Listen to the full podcast interview >

Phase 3 Cushing's Syndrome Trials

LOGICS: A Global Phase 3 Trial in Endogenous Cushing’s Syndrome*

The LOGICS study met its primary endpoint with statistical significance, assessing the safety and efficacy of levoketoconazole in the treatment of endogenous Cushing's syndrome.

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LOGICS Trial Design

  • Double-blind, placebo-controlled, randomized withdrawal following open‑label therapy with levoketoconazole
  • Orally administered study drug
  • Up to 54 subjects will be enrolled in the randomized-withdrawal phase of the study
  • Approximately 40 sites globally
  • Dose titration and maintenance phase to therapeutic dose for levoketoconazole-naïve subjects (14 to 19 weeks)
  • Double-blind randomized withdrawal phase (8 to 9 1/2 weeks)
  • Double-blind restoration phase (8 to 9 1/2 weeks)

The safety and efficacy of levoketoconazole for treatment of endogenous Cushing’s syndrome have not been established.

View additional information on the LOGICS study.

*Cortendo AB (Cortendo), a subsidiary of Strongbridge Biopharma plc, is the sponsor of the LOGICS trial.

SONICS: A Global Phase 3 Trial in Endogenous Cushing’s Syndrome

The SONICS study, now completed, met its primary endpoint, assessing normalization of mUFC at the end of 6 months of maintenance therapy.

3.1_sonics_trialdesign_chart_desktop

SONICS Trial Design2

  • Single-arm, open-label study
  • Orally administered study drug
  • Enrollment goal: 90 patients
  • Approximately 90 sites globally
  • Titrate to therapeutic dose (weeks 2–21)
  • 6-month maintenance phase on therapeutic dose
  • 6-month extended evaluation

The safety and efficacy of levoketoconazole for treatment of endogenous Cushing’s syndrome have not been established.

View additional information on the SONICS study.

Cortendo AB (Cortendo), a subsidiary of Strongbridge Biopharma plc, is the sponsor of the SONICS trial.

OPTICS: A Long-term Global Phase 3 Trial in Endogenous Cushing's Syndrome

The OPTICS study, currently ongoing but closed to new enrollment, is an open-label extension study in those who previously completed either the LOGICS trial, the SONICS trial, or both.

OPTICS Trial Design3

  • Single-arm, open-label extension study
  • Orally administered study drug
  • Approximately 30 sites globally
  • Maintenance of therapeutic dose for up to 3 years

The safety and efficacy of levoketoconazole for treatment of endogenous Cushing’s syndrome have not been established.

Cortendo AB (Cortendo), a subsidiary of Strongbridge Biopharma plc, is the sponsor of the OPTICS trial.

View additional information on the OPTICS study.

Levoketoconazole: A Pure Enantiomer Derived from Ketoconazole

Levoketoconazole is the pure 2S, 4R enantiomer derived from ketoconazole, an adrenal steroidogenesis inhibitor. Ketoconazole is an antifungal drug that has limited data in Cushing's syndrome and is not FDA-approved for treating Cushing's syndrome in the United States. We believe levoketoconazole may have favorable efficacy, safety, and tolerability for patients with endogenous Cushing's syndrome based on our robust, global clinical trial program.

References

  1. Nieman LK, Biller BMK, Findling JW, et al; for the Endocrine Society. Treatment of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100:2807-2831.
  2. Salvatori R, DelConte A, Geer EB, et al. An open-label study to assess the safety and efficacy of levoketoconazole (COR-003) in the treatment of endogenous Cushing’s syndrome. Presented at: The Endocrine Society’s 97th Annual Meeting & Expo; March 6, 2015; San Diego, CA. https://endo.confex.com/endo/2015endo/webprogram/Paper20580.html.
  3. U.S. National Library of Medicine. Open-label treatment in Cushing’s syndrome (OPTICS). Available at: https://clinicaltrials.gov/ct2/show/NCT03621280.