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

October 13, 2022 updated by: Cortendo AB

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
84

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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: 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.
max. 9.5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cortendo AB

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 26, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • COR-2017-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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