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

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ClinicalTrials.gov Identifier: NCT03277690
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Cortendo AB

Brief Summary:
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous CS previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.

Condition or disease Intervention/treatment Phase
Endogenous Cushing's Syndrome Drug: Levoketoconazole Drug: Placebo Phase 3

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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-Controlled, Randomized Withdrawal Following Open Label Therapy Study to Assess the Safety and Efficacy of Levoketoconazole (2S, 4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome
Actual Study Start Date : September 26, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Levoketoconazole
Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo
Drug: Levoketoconazole

During the double-blind Withdrawal Phase, patients will receive up to 1200 mg levoketoconazole daily.

During the double-blind Restoration Phase, patients will receive levoketoconazole plus placebo.

Other Name: COR-003

Placebo Comparator: Placebo
Double blind withdrawal phase: Placebo; Double blind restoration phase: Placebo plus Levoketoconazole
Drug: Placebo

During the double-blind Withdrawal Phase, patients will receive placebo tablets.

During the double-blind Restoration Phase, patients will receive placebo plus levoketoconazole.





Primary Outcome Measures :
  1. 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. [ Time Frame: max. 9.5 weeks ]
    Urinary free cortisol (UFC) level measurement



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277690


Contacts
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Contact: Cortendo AB 610-254-9200 LOGICS@cortendo.com
Contact: Cortendo AB Study Information 610-254-9200 LOGICS@cortendo.com

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Locations
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United States, California
Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital Recruiting
Los Angeles, California, United States, 90033
Contact: Monica Chiu    323-865-1225    monic.chiu@med.usc.edu   
Principal Investigator: John Carmichael         
Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center Recruiting
Los Angeles, California, United States, 90048
Contact: Vivian Hwe, CCRP    424-315-4489    vivian.hwe@cshs.org   
Principal Investigator: Ning-Ai Liu, MD         
UCLA School of Medicine, Medicine/Endocrinology Department Recruiting
Los Angeles, California, United States, 90095
Contact: Abdul Zahid    310-825-5874    AZahid@mednet.ucla.edu   
Principal Investigator: Anthony Heaney, MD, PhD         
United States, Florida
The Center for Diabetes and Endocrine Care Recruiting
Fort Lauderdale, Florida, United States, 33312
Contact: Carie-Ann Silvia    957-963-7191 ext 243    csilvia@diabetes-endocare.com   
Principal Investigator: Sam Lerman, MD         
United States, Georgia
Emory University, Neurosurgery Recruiting
Atlanta, Georgia, United States, 30322
Contact: Emilee Wehunt    404-778-7427    emorga9@emory.edu   
Principal Investigator: Adriana Ioachimescu         
United States, Illinois
Northwestern University, Medicine - Endocrinology Recruiting
Chicago, Illinois, United States, 60611
Contact: Daphne Adelman    312-908-9002    d-adelman@northwestern.edu   
Principal Investigator: Mark Molitch, MD         
United States, Maryland
Johns Hopkins University, Endocrinology Department Recruiting
Baltimore, Maryland, United States, 21287
Contact: Haley Rue    410-955-2812    hrue1@jhmi.edu   
Principal Investigator: Roberto Salvatori, MD         
United States, Michigan
University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Elizabeth Wu, MPH, CCRP    734-764-4048    elizwu@med.umich.edu   
Principal Investigator: Tobias Else, MD         
United States, Missouri
Washington University School of Medicine, Endocrinology Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Traci Bell    314-747-5371    traci.bell@wustl.edu   
Principal Investigator: Julie Silverstein         
United States, New York
Columbia University, College of P&S Medicine/Neuro-endocrine Unit Recruiting
New York, New York, United States, 10032
Contact: Aliza Levin    212-342-4435    al2817@cumc.columbia.edu   
Principal Investigator: Gabrielle Page-Wilson, MD         
Memorial Sloan Kettering Cancer Center, Endocrinology Recruiting
New York, New York, United States, 10065
Contact: Hannah Robins    646-888-1365    robinsh@mskcc.org   
Principal Investigator: Eliza Geer         
United States, Oregon
Oregon Health & Science University, Neurological Surgery Recruiting
Portland, Oregon, United States, 97239
Contact: Jessica Williams    503-494-9546    nelsjess@ohsu.edu   
Principal Investigator: Maria Fleseriu, MD         
United States, Pennsylvania
Allegheny Neuroendocrinology Center, West Penn Allegheny Health System Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Contact: Ann Minnock    412-359-5143    aminnock@aghendo.com   
Principal Investigator: Murray Gordon         
United States, Tennessee
Midstate Endocrine Associates - Endocrinology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jesselyn Jerkins    615-329-5029    msearesarch@gmail.com   
Principal Investigator: Terri Jerkins, MD         
Bulgaria
Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases Recruiting
Sofia, Bulgaria, 1431
Contact: Deniz Bakalov, MD    +00359 888 956479    dbakalov@abv.bg   
Principal Investigator: Zdravko Kamenov, MD PhD DMSc         
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases Recruiting
Sofia, Bulgaria, 1431
Contact: Maria Miteva, MD    +359889242566    m_miteva@yahoo.com   
Principal Investigator: Maria Orbetzova, MD PhD DMSc         
University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika Recruiting
Sofia, Bulgaria, 1431
Contact: Atanaska Elenkova    +35988719801    atanaskae@gmail.com   
Principal Investigator: Sabina Zharieva, MD, DMsc         
Denmark
Rigshospitalet, Copenhagen University Hospital, Endocrinology Department Withdrawn
Copenhagen, Denmark, 2100
France
APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques Recruiting
Marseille, Cedex 5, France, 13385
Contact: Mona Sahnoun    +33 491383375    mouna.sahnoun@ap-hm.fr   
Principal Investigator: Thierry Brue         
Greece
Evangelismos Athens General Hospital, Department of Endocrinology Recruiting
Athens, Greece, 10676
Contact: Dimitra Vassiliadi    +302132041825    dimitravas@gmail.com   
Principal Investigator: Stylianos Tsagarakis         
General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre Recruiting
Athens, Greece, 11527
Contact: Athina Markou    +306972029389    amarkouuk@yahoo.co.uk   
Principal Investigator: Theodora Kounadi         
General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology" Recruiting
Athens, Greece, 11527
Contact: Marina Tasoli    +306972692962    martso.mt@gmail.com   
Principal Investigator: Gregory Kaltsas         
University General Hospital of Ioannina, Department of Endocrinology Recruiting
Ioánnina, Greece, 45110
Contact: Maria Christou    +302651099734    mariachristou1@gmail.com   
Principal Investigator: Stelios Tigas         
Hippokration General Hospital, "Endocrinology and Diabetes Department Recruiting
Thessaloníki, Greece, 54642
Contact: Paraskevi Komzia    +306932311009    Voulak2008@hotmail.com   
Principal Investigator: Fontini Adamidou         
Hungary
Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor Recruiting
Budapest, Hungary, 1088
Contact: Judith Toke    +36-20-663-2908    tokejudit@hotmail.com   
Principal Investigator: Miklos Toth         
Israel
Bnai Zion Medical Center, Institute of Endocrinology Recruiting
Haifa, Israel, 34802
Contact: Michal Yeiches    +972528283062    yeiches@gmail.com   
Principal Investigator: Leonard Saiegh         
Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus" Recruiting
Petach Tikva, Israel, 49100
Contact: Liat Rot    +9723921 1403    liatro3@clalit.org.il   
Principal Investigator: Ilan Shimon         
Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension Recruiting
Tel Aviv, Israel, 642-3906
Contact: Miri Margaliot    +972-3-697 4243    mirim@tlvmc.gov.il   
Principal Investigator: Yona Greenman         
Italy
Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche Recruiting
Ancona, Italy, 60126
Contact: Giorgio Arnaldi    +39 335 837 3859    g.arnaldi@ospedaliriuniti.marche.it   
Principal Investigator: Giorgio Arnaldi         
University of Genova, Department of Internal Medicine & Medical Specialties (DiMI) Recruiting
Genova, Italy, 16132
Contact: Federico Gatto    +39 010 353 8886    fedgatto@hotmail.it   
Principal Investigator: Diego Ferone         
AOU Policlinico G. Martino Sezione di Endocrinologia Recruiting
Messina, Italy, 98125
Contact: Maria Lusia Tindara Torre    3474777015    marialuisatorre78@libero.it   
Principal Investigator: Salvatore Cannavo         
AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano) Recruiting
Napoli, Italy, 8031
Contact: Maria Cristina De Martino    +393289622955    demartino.mc@gmail.com   
Principal Investigator: Rosario Pivonello         
Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology Recruiting
Roma, Italy, 00168
Contact: Pietro Locantore    +39 328 828 2256    pietro.locantore@icloud.com   
Principal Investigator: Alfredo Pontecorvi         
Policlinico Universitario Sant'Andrea, Scienze Mediche Recruiting
Roma, Italy, 00189
Contact: Pina Lardo    +390633775597    pina85la@gmail.com   
Principal Investigator: Vincenzo Toscano         
AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo Recruiting
Torino, Italy, 10126
Contact: Valeria Cambria    +39(0) 116 335 544    valeriacambria@alice.it   
Principal Investigator: Roberta Giordano         
Netherlands
Leiden University, Leiden University Medical Center, Department of Endocrinology Recruiting
Leiden, Netherlands, 2333ZA
Contact: Sabrina Hendriksen    +31 715 263 082    s.hendriksen@lumc.nl   
Principal Investigator: Nienke Biermasz         
Erasmus Medical Center, Department of Internal Medicine Recruiting
Rotterdam, Netherlands, 3015CE
Contact: Sjaan Poldermans    +31 (0)10 703 1598    b.poldermans@erasmusmc.nl   
Principal Investigator: Richard Feelders         
Poland
Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department Recruiting
Gliwice, Poland, 44-101
Contact: Jolanta Krajewska    +48 322789301    Jolanta.krajewska@io.gliwice.pl   
Principal Investigator: Barbara Jarząb         
Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych Recruiting
Warsaw, Poland, 04-141
Contact: Martha Mazur    +48 261 818 058    mimazur@wim.mil.pl   
Principal Investigator: Przemyslaw Witek         
Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych Recruiting
Łódź, Poland, 93-338
Contact: Magdalena Stasiak    +48 502 049 292    mstasiak33@gmail.com   
Principal Investigator: Andrzej Lewinski         
Romania
Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie Recruiting
Târgu-Mureş, Mures, Romania, 540072
Contact: Adelina Micheu       adelina_micheu@yahoo.com   
Principal Investigator: Maria Ionela Pascanu         
Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie Recruiting
Timişoara, Timis, Romania, 300723
Contact: Daniela Amzar    +4074469-0639    dana_amzar@yahoo.com   
Principal Investigator: Melania-Olga Balas         
Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie Recruiting
Bucuresti, Romania, 011863
Contact: Monica Gheorghiu    +40723298230    monicagheorghiu@yahoo.com   
Principal Investigator: Corin Badiu         
Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie Recruiting
Cluj-Napoca, Romania, 400349
Contact: Alina Silaghi       alinasilaghi@yahoo.com   
Principal Investigator: Carmen Emanuela Georgescu         
Spain
Hospital Universidad De La Ribera, Endocrinologia Recruiting
Alzira, Valencia, Spain, 46600
Contact: Maria Angeles Martorell    +34962458580    mamartorell@hospital-ribera.com   
Principal Investigator: Carmen Fajardo         
Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition Recruiting
Madrid, Spain, 28034
Contact: Elena Fernández Durán    +34913368056    elena.fernandezd@salud.madrid.org   
Principal Investigator: Manuel Luque Ramirez         
Sponsors and Collaborators
Cortendo AB
Investigators
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Study Director: Steven Schoenfeld, MD Cortendo AB

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Responsible Party: Cortendo AB
ClinicalTrials.gov Identifier: NCT03277690     History of Changes
Other Study ID Numbers: COR-2017-01
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cortendo AB:
Cushing Syndrome, Adrenocortical Hyperfunction
Additional relevant MeSH terms:
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Cushing Syndrome
Syndrome
Disease
Pathologic Processes
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases