Open-label Treatment in Cushing's Syndrome (OPTICS)

An Open-label Extension Study of Levoketoconazole (2S,4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome

This is a long-term, open-label extension study of levoketoconazole in subjects with endogenous Cushing's Syndrome.

Study Overview

• Status: Completed
• Conditions: Cushing Syndrome; Cushing Disease
• Intervention / Treatment: Drug: Levoketoconazole

Detailed Description

This is a long-term, OLE study of levoketoconazole in subjects with endogenous CS who have completed one or both parent studies or otherwise potentially qualify for this study, as defined in the eligibility criteria.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Sveti Georgy University Hospital Clinic of Endocrinology and Metabolic Diseases
  • Sofia, Bulgaria, 1431
    • Alexandovska University Hospital
  • Sofia, Bulgaria, 1431
    • University Specialized Hospital for Active Treatment in Endocrinology
• France
  • Marseille, France, 13385
    • APHM Hôpital de la Conception
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evangelismos Department of Endocrinology and Diabete
  • Thessaloníki, Greece, 54642
    • Hippokration General Hospital Endocrinology and Diabetes Department
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem II. Belgyógyászati Klinika
• Israel
  • Haifa, Israel, 34802
    • Bnai Zion Medical Center Endocrinology Institute
  • Petah tikva, Israel, 49100
    • Rabin Medical Center, Beilinson Campus
  • Tel Aviv, Israel, 6423906
    • Tel Aviv-Sourasky Medical Center Institute Endocrinology Metabolism & Hypertension
• Italy
  • Ancona, Italy, 60126
    • Clinica Endocrinologia malattie del Metabolismo
  • Messina, Italy, 98125
    • AOU Policlinico G. Martino Sezione di Endocrinologia
  • Naples, Italy, 80131
    • Via Sergio Pansini 5 Uni Naples FedericoII Dept of Molecular&Clinical Endocrinology&Oncology
  • Roma, Italy, 00189
    • Policlinico Universitario Sant'Andrea
  • Turin, Italy, 10126
    • University of Turin
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medical Center
• Poland
  • Łódź, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
• Romania
  • Cluj-Napoca, Romania, 400349
    • Institutul National de Endocrinologie C.I. Parhon
  • Cluj-Napoca, Romania, 400349
    • Spitalul Clinic Judetean de Urgenta Cluj-Napoca
  • Târgu-Mureş, Romania, 540139
    • Spitalul Clinic Judetean Mures
• Spain
  • Alzira, Spain, 46600
    • Hospital Universidad De La Ribera
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33312
      • The Center for Diabetes and Endocrine Care
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico HSC - HSC Sponsored Projects Office
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Completed the Extended Evaluation Phase of Study COR-2012-01 (i.e. M12)

2. Completed the Restoration Phase of Study COR-2017-01 (i.e. RES2)

   NOTE: Subjects meeting criteria 1 or 2 above who have had a break in therapy may be eligible only after discussion with the Medical Monitor. If eligible, such subjects may require re-establishment of the Therapeutic Dose via titration. All subjects who have had a break in therapy should be discussed with the Medical Monitor to determine the starting dose of levoketoconazole. Prior to resuming treatment with levoketoconazole, other therapies for Cushing's Syndrome must undergo an appropriate washout period, with minimum durations as follows:

   • Ketoconazole or metyrapone: 2 weeks;
   • Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks);
   • Octreotide acetate LAR, lanreotide Autogel, pasireotide LAR: 12 weeks;
   • Lanreotide SR: 8 weeks;
   • Octreotide acetate (immediate release) or short-acting pasireotide: 1 week;
   • Mifepristone (RU 486, KORLYM): 4 weeks;
   • Megestrol acetate or medroxyprogesterone acetate (and selected other synthetic progestins): 6 weeks.
3. Currently in a named patient program or other Expanded Access Program receiving levoketoconazole
4. Were levoketoconazole-naïve prior to entry and received early rescue therapy with open-label levoketoconazole in Study COR-2017-01.
5. Achieved a clinically meaningful partial response (with reduction of UFC) in Study COR-2017-01 at dose level 7 or at a maximally tolerated dose of levoketoconazole but did not meet the randomization criteria for Study COR-2017-01 at the end of the Dose Titration and Maintenance Phase when randomization was open.
6. Were levoketoconazole-naïve prior to entry and were enrolled in Study COR-2017-01 in the Dose Titration and Maintenance Phase when randomization was closed. (NOTE: Such subjects must receive at least 1 dose of levoketoconazole before transitioning to this study.)

Exclusion Criteria:

1. Discontinued levoketoconazole while participating in Study COR-2012-01 or Study COR-2017-01 or a named patient program or other Expanded Access program, due to safety or tolerability concerns or lack of efficacy.
2. Scheduled for surgery for treatment of CS or received surgery for treatment of CS within the 6 weeks prior to Screening.
3. Treated with mitotane within 6 months prior to enrollment.
4. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levoketoconazole; Levoketoconazole taken twice daily up to 1200 mg daily	Drug: Levoketoconazole; Levoketoconazole up to 1200 mg daily; Other Names: COR-003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from Baseline in 24-h UFC	Changes or shifts from baseline in mUFC	From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
Changes from Baseline in Late Night Salivary Cortisol	Changes or shifts from baseline in late night salivary cortisol levels	From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.
Changes from Baseline in AEs/SAEs/AESI as assessed by CTCAE V4.03	Changes from Baseline in the incidence and severity of AEs, SAEs, AESIs	From Baseline to final study visit or up to a maximum of 3 years, whichever comes first.

Collaborators and Investigators

• Sponsor: Cortendo AB
• Investigators: Study Chair: Fredric Cohen, MD, Cortendo AB

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: August 3, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Disease; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Pituitary Neoplasms; Syndrome; Cushing Syndrome; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
• Other Study ID Numbers: COR-2017-OLE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No