Open-label Treatment in Cushing's Syndrome

Cushing Syndrome Clinical Trial

— OPTICS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03621280
• Other study ID #: COR-2017-OLE
• Status: Completed
• Phase: Phase 3
• Start date: January 7, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2023
• Source: Cortendo AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Cushing Disease
• Cushing Syndrome
• Pituitary ACTH Hypersecretion
• Syndrome

Intervention

Drug:
• Levoketoconazole
Levoketoconazole up to 1200 mg daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cortendo AB

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.