A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing's Syndrome.
- Conditions
- Endogenous Cushing's Syndrome
- Interventions
- Drug: PlaceboDrug: Levoketoconazole
- Registration Number
- NCT03277690
- Lead Sponsor
- Cortendo AB
- 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
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- 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
Trial Locations
- Locations (45)
University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND
🇺🇸Ann Arbor, Michigan, United States
Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych
🇵🇱Warsaw, Poland
Evangelismos Athens General Hospital, Department of Endocrinology
🇬🇷Athens, Greece
Bnai Zion Medical Center, Institute of Endocrinology
🇮🇱Haifa, Israel
Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases
🇧🇬Sofia, Bulgaria
AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo
🇮🇹Torino, Italy
Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie
🇷🇴Târgu-Mureş, Mures, Romania
Oregon Health & Science University, Neurological Surgery
🇺🇸Portland, Oregon, United States
Policlinico Universitario Sant'Andrea, Scienze Mediche
🇮🇹Roma, Italy
Columbia University, College of P&S Medicine/Neuro-endocrine Unit
🇺🇸New York, New York, United States
General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology"
🇬🇷Athens, Greece
Hippokration General Hospital, "Endocrinology and Diabetes Department
🇬🇷Thessaloníki, Greece
Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche
🇮🇹Ancona, Italy
AOU Policlinico G. Martino Sezione di Endocrinologia
🇮🇹Messina, Italy
APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques
🇫🇷Marseille, Cedex 5, France
Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension
🇮🇱Tel Aviv, Israel
Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie
🇷🇴Bucuresti, Romania
Leiden University, Leiden University Medical Center, Department of Endocrinology
🇳🇱Leiden, Netherlands
AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano)
🇮🇹Napoli, Italy
Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology
🇮🇹Roma, Italy
Rigshospitalet, Copenhagen University Hospital, Endocrinology Department
🇩🇰Copenhagen, Denmark
Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor
🇭🇺Budapest, Hungary
University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika
🇧🇬Sofia, Bulgaria
Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie
🇷🇴Timişoara, Timis, Romania
Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie
🇷🇴Cluj-Napoca, Romania
Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition
🇪🇸Madrid, Spain
Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center
🇺🇸Los Angeles, California, United States
UCLA School of Medicine, Medicine/Endocrinology Department
🇺🇸Los Angeles, California, United States
The Center for Diabetes and Endocrine Care
🇺🇸Fort Lauderdale, Florida, United States
Allegheny Neuroendocrinology Center, West Penn Allegheny Health System
🇺🇸Pittsburgh, Pennsylvania, United States
Emory University, Neurosurgery
🇺🇸Atlanta, Georgia, United States
Northwestern University, Medicine - Endocrinology
🇺🇸Chicago, Illinois, United States
Johns Hopkins University, Endocrinology Department
🇺🇸Baltimore, Maryland, United States
General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre
🇬🇷Athens, Greece
University General Hospital of Ioannina, Department of Endocrinology
🇬🇷Ioánnina, Greece
Memorial Sloan Kettering Cancer Center, Endocrinology
🇺🇸New York, New York, United States
Washington University School of Medicine, Endocrinology
🇺🇸Saint Louis, Missouri, United States
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases
🇧🇬Sofia, Bulgaria
Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus"
🇮🇱Petach Tikva, Israel
University of Genova, Department of Internal Medicine & Medical Specialties (DiMI)
🇮🇹Genova, Italy
Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department
🇵🇱Gliwice, Poland
Erasmus Medical Center, Department of Internal Medicine
🇳🇱Rotterdam, Netherlands
Hospital Universidad De La Ribera, Endocrinologia
🇪🇸Alzira, Valencia, Spain
Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych
🇵🇱Łódź, Poland