Open-label Treatment in Cushing's Syndrome

Phase 3

Completed

• Conditions: Cushing Syndrome; Cushing Disease
• Interventions: Drug: Levoketoconazole

• Registration Number: NCT03621280
• Lead Sponsor: Cortendo AB

Brief Summary

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

Detailed Description

This is a long-term, open-label extension (OLE) study of levoketoconazole in participants with endogenous Cushing's Syndrome (CS) who have completed one or both parent studies or otherwise potentially qualify for this study, as defined in the eligibility criteria.

Study Timeline

• Study First Submitted: 2018-05-18
• Study First Submitted QC: 2018-08-03
• Study First Posted: 2018-08-08
• Study Start: 2019-01-07
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2025-06
• Results First Submitted: 2025-06-04
• Results First Submitted QC: 2025-06-04
• Last Update Submitted: 2025-06-04
• Results First Posted: 2025-06-19
• Last Update Posted: 2025-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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: Participants 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 participants may require re-establishment of the Therapeutic Dose via titration. All participants 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.)

Key

Exclusion Criteria

• 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.
• Scheduled for surgery for treatment of CS or received surgery for treatment of CS within the 6 weeks prior to Screening.
• Treated with mitotane within 6 months prior to 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Levoketoconazole	Levoketoconazole	Levoketoconazole taken twice daily up to 1200 mg daily

Primary Outcome Measures

Name	Time	Method
Proportions of Participants With Mean Urinary Free Cortisol (mUFC) Categorization Based on Upper Limit of Normal (ULN)	From parent study Baseline to final study visit or up to a maximum of 3 years, whichever comes first.	Proportions of participants with mUFC: 1) Less or equal to the ULN of the reference range, 2) Above the ULN to 1.5x the ULN, and 3) Above 1.5x the ULN.

Trial Locations

Locations (30)

The Center for Diabetes and Endocrine Care; 🇺🇸 Fort Lauderdale, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

University of New Mexico HSC - HSC Sponsored Projects Office; 🇺🇸 Albuquerque, New Mexico, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Sveti Georgy University Hospital Clinic of Endocrinology and Metabolic Diseases; 🇧🇬 Plovdiv, Bulgaria

Alexandovska University Hospital; 🇧🇬 Sofia, Bulgaria

Scroll for more (20 remaining)