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

• ClinicalTrials.gov Identifier: NCT03621280
• Recruitment Status: Active, not recruiting
• First Posted: August 8, 2018
• Last Update Posted: August 3, 2021
• Sponsor: Cortendo AB
• Information provided by (Responsible Party): Cortendo AB

Tracking Information

• First Submitted Date: May 18, 2018
• First Posted Date: August 8, 2018
• Last Update Posted Date: August 3, 2021
• Actual Study Start Date: January 7, 2019
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2018)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Open-label Treatment in Cushing's Syndrome
• Official Title: An Open-label Extension Study of Levoketoconazole (2S,4R-ketoconazole) in the Treatment of Endogenous Cushing's Syndrome
• Brief Summary: This is a long-term, open-label extension study of levoketoconazole in subjects with endogenous Cushing's Syndrome.
• 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
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open-Label Extension Study

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Cushing Syndrome
• Cushing Disease

Intervention

Drug: Levoketoconazole

Levoketoconazole up to 1200 mg daily

Other Name: COR-003

Study Arms

Experimental: Levoketoconazole

Levoketoconazole taken twice daily up to 1200 mg daily

Intervention: Drug: Levoketoconazole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 3, 2018): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, France, Greece, Hungary, Israel, Italy, Netherlands, Poland, Romania, Spain, United States
• Removed Location Countries: Denmark, Turkey

Administrative Information

• NCT Number: NCT03621280
• Other Study ID Numbers: COR-2017-OLE
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Cortendo AB
• Original Responsible Party: Same as current
• Current Study Sponsor: Cortendo AB
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Fredric Cohen, MD; Cortendo AB

• PRS Account: Cortendo AB
• Verification Date: August 2021