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

NCT ID: NCT03277690

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-26
• Study Completion Date: 2020-08-31

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.

Conditions

Endogenous Cushing's Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levoketoconazole

Double blind withdrawal phase: Levoketoconazole (up to a dose of 1200 mg); Double blind restoration phase: Levoketoconazole plus Placebo

Group Type: EXPERIMENTAL

Levoketoconazole

Intervention Type: DRUG

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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

COR-003

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cortendo AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier Valencia, MD

Role: STUDY_DIRECTOR

Cortendo AB

Locations

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

Emory University, Neurosurgery

Atlanta, Georgia, United States

Northwestern University, Medicine - Endocrinology

Chicago, Illinois, United States

Johns Hopkins University, Endocrinology Department

Baltimore, Maryland, United States

University of Michigan, Comprehensive Endocrine Research, Internal Medicine - MEND

Ann Arbor, Michigan, United States

Washington University School of Medicine, Endocrinology

St Louis, Missouri, United States

Columbia University, College of P&S Medicine/Neuro-endocrine Unit

New York, New York, United States

Memorial Sloan Kettering Cancer Center, Endocrinology

New York, New York, United States

Oregon Health & Science University, Neurological Surgery

Portland, Oregon, United States

Allegheny Neuroendocrinology Center, West Penn Allegheny Health System

Pittsburgh, Pennsylvania, United States

Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD Clinic of Endocrinology and Metabolic Diseases

Sofia, , Bulgaria

University Specialized Hospital for Active Treatment in Endocrinology (USHATE) I Klinika

Sofia, , Bulgaria

Rigshospitalet, Copenhagen University Hospital, Endocrinology Department

Copenhagen, , Denmark

APHM Hôpital de la Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques

Marseille, Cedex 5, France

Evangelismos Athens General Hospital, Department of Endocrinology

Athens, , Greece

General Hospital of Athens 'G. Gennimatas', Department of Endocrinology-Diabetes Centre

Athens, , Greece

General Hospital of Athens 'Laiko', "National and Kapodistrian University of Athens Medical School Pathophysiology - Endocrinology"

Athens, , Greece

University General Hospital of Ioannina, Department of Endocrinology

Ioannina, , Greece

Hippokration General Hospital, "Endocrinology and Diabetes Department

Thessaloniki, , Greece

Semmelweis Egyetem II. Belgyógyászati Klinika A.épület I.emelet ODM-labor

Budapest, , Hungary

Bnai Zion Medical Center, Institute of Endocrinology

Haifa, , Israel

Rabin Medical Center- Beilinson Hospital, "Institute of Endocrinology & Metabolism, Beilinson Campus"

Petah Tikva, , Israel

Tel-Aviv Sourasky Medical Center Institute of Endocrinology, Metabolism and Hypertension

Tel Aviv, , Israel

Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche

Ancona, , Italy

University of Genova, Department of Internal Medicine & Medical Specialties (DiMI)

Genova, , Italy

AOU Policlinico G. Martino Sezione di Endocrinologia

Messina, , Italy

AOU Federico II, Sezione di Endocrinologia (Edificio 1, Secondo Piano)

Napoli, , Italy

Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology

Roma, , Italy

Policlinico Universitario Sant'Andrea, Scienze Mediche

Roma, , Italy

AOU Citta della Salure e della Scienza SC Endocrinologia, Diabetologia e Metabolismo

Torino, , Italy

Leiden University, Leiden University Medical Center, Department of Endocrinology

Leiden, , Netherlands

Erasmus Medical Center, Department of Internal Medicine

Rotterdam, , Netherlands

Maria Sklodowska-Curie Memorial Institute - Cancer Center Gliwice Branch, Nuclear Medicine and Endocrine Oncology Department

Gliwice, , Poland

Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych

Lodz, , Poland

Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych

Warsaw, , Poland

Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie

Târgu Mureş, Mureș County, Romania

Spitalul Clinic Judetean de Urgenta "Pius Brinzeu", Departamentul de Endocrinologie

Timișoara, Timiș County, Romania

Institutul National de Endocrinologie C.I. Parhon, Sectia Clinica de Endocrinologie II, Patologia tiroidei de corelatie

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Sectia Clinica Endocrinologie

Cluj-Napoca, , Romania

Hospital Universidad De La Ribera, Endocrinologia

Alzira, Valencia, Spain

Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition

Madrid, , Spain

Countries

United States; Bulgaria; Denmark; France; Greece; Hungary; Israel; Italy; Netherlands; Poland; Romania; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

COR-2017-01

Identifier Type: -

Identifier Source: org_study_id