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

Sponsor
Cortendo AB (Industry)
Overall Status
Completed
CT.gov ID
NCT03277690
Collaborator
(none)
44
Enrollment
45
Locations
2
Arms
35.2
Actual Duration (Months)
1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Actual Enrollment :
44 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 :
Sep 26, 2017
Actual Primary Completion Date :
Jun 30, 2020
Actual Study Completion Date :
Aug 31, 2020

Arms and Interventions

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 Names:
  • 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.

    Outcome Measures

    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. [max. 9.5 weeks]

      Urinary free cortisol (UFC) level measurement

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital Los Angeles California United States 90033
    2 Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center Los Angeles California United States 90048
    3 UCLA School of Medicine, Medicine/Endocrinology Department Los Angeles California United States 90095
    4 The Center for Diabetes and Endocrine Care Fort Lauderdale Florida United States 33312
    5 Emory University, Neurosurgery Atlanta Georgia United States 30322
    6 Northwestern University, Medicine - Endocrinology Chicago Illinois United States 60611
    7 Johns Hopkins University, Endocrinology Department Baltimore Maryland United States 21287
    8 University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND Ann Arbor Michigan United States 48109
    9 Washington University School of Medicine, Endocrinology Saint Louis Missouri United States 63110
    10 Columbia University, College of P&S Medicine/Neuro-endocrine Unit New York New York United States 10032
    11 Memorial Sloan Kettering Cancer Center, Endocrinology New York New York United States 10065
    12 Oregon Health & Science University, Neurological Surgery Portland Oregon United States 97239
    13 Allegheny Neuroendocrinology Center, West Penn Allegheny Health System Pittsburgh Pennsylvania United States 15212
    14 Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases Sofia Bulgaria 1431
    15 University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases Sofia Bulgaria 1431
    16 University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika Sofia Bulgaria 1431
    17 Rigshospitalet, Copenhagen University Hospital, Endocrinology Department Copenhagen Denmark 2100
    18 APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques Marseille Cedex 5 France 13385
    19 Evangelismos Athens General Hospital, Department of Endocrinology Athens Greece 10676
    20 General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre Athens Greece 11527
    21 General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology" Athens Greece 11527
    22 University General Hospital of Ioannina, Department of Endocrinology Ioánnina Greece 45110
    23 Hippokration General Hospital, "Endocrinology and Diabetes Department Thessaloníki Greece 54642
    24 Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor Budapest Hungary 1088
    25 Bnai Zion Medical Center, Institute of Endocrinology Haifa Israel 34802
    26 Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus" Petach Tikva Israel 49100
    27 Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension Tel Aviv Israel 642-3906
    28 Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche Ancona Italy 60126
    29 University of Genova, Department of Internal Medicine & Medical Specialties (DiMI) Genova Italy 16132
    30 AOU Policlinico G. Martino Sezione di Endocrinologia Messina Italy 98125
    31 AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano) Napoli Italy 8031
    32 Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology Roma Italy 00168
    33 Policlinico Universitario Sant'Andrea, Scienze Mediche Roma Italy 00189
    34 AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo Torino Italy 10126
    35 Leiden University, Leiden University Medical Center, Department of Endocrinology Leiden Netherlands 2333ZA
    36 Erasmus Medical Center, Department of Internal Medicine Rotterdam Netherlands 3015CE
    37 Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department Gliwice Poland 44-101
    38 Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych Warsaw Poland 04-141
    39 Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych Łódź Poland 93-338
    40 Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie Târgu-Mureş Mures Romania 540072
    41 Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie Timişoara Timis Romania 300723
    42 Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie Bucuresti Romania 011863
    43 Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie Cluj-Napoca Romania 400349
    44 Hospital Universidad De La Ribera, Endocrinologia Alzira Valencia Spain 46600
    45 Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition Madrid Spain 28034

    Sponsors and Collaborators

    • Cortendo AB

    Investigators

    • Study Director: Xavier Valencia, MD, Cortendo AB

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Cortendo AB
    ClinicalTrials.gov Identifier:
    NCT03277690
    Other Study ID Numbers:
    • COR-2017-01
    First Posted:
    Sep 11, 2017
    Last Update Posted:
    Mar 16, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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:
    Cushing Syndrome
    Syndrome

    Study Results

    No Results Posted as of Mar 16, 2021