A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.
Endogenous Cushing's Syndrome
About this trial
This is an interventional treatment trial for Endogenous Cushing's Syndrome focused on measuring Cushing Syndrome, Adrenocortical Hyperfunction
Eligibility Criteria
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.
Sites / Locations
- Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital
- Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center
- UCLA School of Medicine, Medicine/Endocrinology Department
- The Center for Diabetes and Endocrine Care
- Emory University, Neurosurgery
- Northwestern University, Medicine - Endocrinology
- Johns Hopkins University, Endocrinology Department
- University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND
- Washington University School of Medicine, Endocrinology
- Columbia University, College of P&S Medicine/Neuro-endocrine Unit
- Memorial Sloan Kettering Cancer Center, Endocrinology
- Oregon Health & Science University, Neurological Surgery
- Allegheny Neuroendocrinology Center, West Penn Allegheny Health System
- Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases
- University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases
- University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika
- Rigshospitalet, Copenhagen University Hospital, Endocrinology Department
- APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques
- Evangelismos Athens General Hospital, Department of Endocrinology
- General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre
- General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology"
- University General Hospital of Ioannina, Department of Endocrinology
- Hippokration General Hospital, "Endocrinology and Diabetes Department
- Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor
- Bnai Zion Medical Center, Institute of Endocrinology
- Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus"
- Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension
- Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche
- University of Genova, Department of Internal Medicine & Medical Specialties (DiMI)
- AOU Policlinico G. Martino Sezione di Endocrinologia
- AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano)
- Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology
- Policlinico Universitario Sant'Andrea, Scienze Mediche
- AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo
- Leiden University, Leiden University Medical Center, Department of Endocrinology
- Erasmus Medical Center, Department of Internal Medicine
- Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department
- Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych
- Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych
- Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie
- Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie
- Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie
- Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie
- Hospital Universidad De La Ribera, Endocrinologia
- Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Levoketoconazole
Placebo
Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo
Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole