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

NCT03277690 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: COR-2017-01
• Study Type: interventional
• Target: 84
• Locations: 12 countries
• Sites: 45

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.

Conditions

Endogenous Cushing's Syndrome

Keywords

Cushing Syndrome, Adrenocortical Hyperfunction

Outcome Measures

Primary Outcomes (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.

  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

Study Arms (2)

Levoketoconazole

EXPERIMENTAL

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

Drug: Levoketoconazole

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Levoketoconazole 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.

Also known as: COR-003

Levoketoconazole

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cortendo AB: lead

Study Sites (45)

Keck Medical Center University of Southern California HCII, Internal Medicine - Keck Hospital

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center, Cedars-Sinai Pituitary Center

Los Angeles, California, 90048, United States

Location

UCLA School of Medicine, Medicine/Endocrinology Department

Los Angeles, California, 90095, United States

Location

The Center for Diabetes and Endocrine Care

Fort Lauderdale, Florida, 33312, United States

Location

Emory University, Neurosurgery

Atlanta, Georgia, 30322, United States

Location

Northwestern University, Medicine - Endocrinology

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University, Endocrinology Department

Baltimore, Maryland, 21287, United States

Location

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

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine, Endocrinology

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center, Endocrinology

New York, New York, 10065, United States

Location

Oregon Health & Science University, Neurological Surgery

Portland, Oregon, 97239, United States

Location

Allegheny Neuroendocrinology Center, West Penn Allegheny Health System

Pittsburgh, Pennsylvania, 15212, United States

Location

Alexandovska University Hospital, Clinic of Endocrinology & Metabolic Diseases

Sofia, 1431, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

Rigshospitalet, Copenhagen University Hospital, Endocrinology Department

Copenhagen, 2100, Denmark

Location

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

Marseille, Cedex 5, 13385, France

Location

Evangelismos Athens General Hospital, Department of Endocrinology

Athens, 10676, Greece

Location

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

Athens, 11527, Greece

Location

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

Athens, 11527, Greece

Location

University General Hospital of Ioannina, Department of Endocrinology

Ioannina, 45110, Greece

Location

Hippokration General Hospital, "Endocrinology and Diabetes Department

Thessaloniki, 54642, Greece

Location

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

Budapest, 1088, Hungary

Location

Bnai Zion Medical Center, Institute of Endocrinology

Haifa, 34802, Israel

Location

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

Petah Tikva, 49100, Israel

Location

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

Tel Aviv, 642-3906, Israel

Location

Clinica di Endocrinologia e malattie del Metabolismo, Dipartimento Specialità Mediche

Ancona, 60126, Italy

Location

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

Genova, 16132, Italy

Location

AOU Policlinico G. Martino Sezione di Endocrinologia

Messina, 98125, Italy

Location

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

Napoli, 8031, Italy

Location

Policlinico Agostino Gemelli, Università Cattolica del Sacro Cuore, Endocrinology

Roma, 00168, Italy

Location

Policlinico Universitario Sant'Andrea, Scienze Mediche

Roma, 00189, Italy

Location

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

Torino, 10126, Italy

Location

Leiden University, Leiden University Medical Center, Department of Endocrinology

Leiden, 2333ZA, Netherlands

Location

Erasmus Medical Center, Department of Internal Medicine

Rotterdam, 3015CE, Netherlands

Location

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

Gliwice, 44-101, Poland

Location

Instytut Centrum Zdrowia Matki Polki, Oddział Endokrynologii i Chorób Metabolicznych

Lodz, 93-338, Poland

Location

Wojskowy Instytut Medyczny, Klinika Gastroenterologii, Endokrynologii I Chorob Wewnetrznych

Warsaw, 04-141, Poland

Location

Spitalul Clinic Judetean Mures, Compartimentul de Endocrinologie

Târgu Mureş, Mureș County, 540072, Romania

Location

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

Timișoara, Timiș County, 300723, Romania

Location

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

Bucharest, 011863, Romania

Location

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

Cluj-Napoca, 400349, Romania

Location

Hospital Universidad De La Ribera, Endocrinologia

Alzira, Valencia, 46600, Spain

Location

Hospital Universitario Ramón y Cajal, Endocrinology and Nutrition

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Cushing Syndrome; Adrenocortical Hyperfunction

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Xeris Medical Director
• Organization: Cortendo AB

LOGICS@cortendo.com

+1 610-254-9200

Study Officials

• Xavier Valencia, MD

  Cortendo AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: September 26, 2017
• Primary Completion: June 30, 2020
• Study Completion: August 31, 2020
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); RO (4); HU (1); GR (5); IL (3); US (13); BU (3); DK (1); IT (7); PL (3); FR (1); ES (2)