An Extension Study of CORLUX in the Treatment of Endogenous Cushing's Syndrome

• ClinicalTrials.gov Identifier: NCT00936741
• Recruitment Status: Completed
• First Posted: July 10, 2009
• Results First Posted: April 2, 2014
• Last Update Posted: April 2, 2014
• Sponsor: Corcept Therapeutics
• Information provided by (Responsible Party): Corcept Therapeutics

Tracking Information

• First Submitted Date: July 9, 2009
• First Posted Date: July 10, 2009
• Results First Submitted Date: September 18, 2013
• Results First Posted Date: April 2, 2014
• Last Update Posted Date: April 2, 2014
• Study Start Date: July 2009
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2014)

Number of Participants With Adverse Events [ Time Frame: Up to three years. ]

Subjects who received at least one dose of mifepristone were included in the safety analysis.

• Original Primary Outcome Measures (submitted: July 9, 2009): Long term safety of mifepristone treatment [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: February 19, 2014)

The Long-term Benefit of Mifepristone Treatment in Cushing's Syndrome as Measured by Changes in the Score on the Physician's Global Assessment of Disease Severity [ Time Frame: Up to three years. ]

The mean Investigator's rating of the change in subject's signs and symptoms of Cushing's syndrome from Baseline (Entry into C1073-415) to Endpoint on the Physician's Global Assessment of Disease Severity was ranked on a 9-point scale (9 = much worse, 7 = worse, 5 = no change, 3 = better, 1 = much better). Higher scores indicate more severe illness. Scoring was done at all visits except the 6 Week Follow-up visit; the final visit result (Endpoint) is reported here. The instruction was "Rate the change in the subject's signs and symptoms of Cushing's from Baseline (1 = much better to 9 = much worse)".

• Original Secondary Outcome Measures (submitted: July 9, 2009): Persistence of therapeutic benefit due to continued mifepristone treatment [ Time Frame: 12 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study of CORLUX in the Treatment of Endogenous Cushing's Syndrome
• Official Title: An Open Label Extension Study of the Efficacy and Safety of CORLUX® (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome
• Brief Summary: Participants in study C-1073-400 (NCT00569582) will be invited to participate in this extension study to examine the long term safety of mifepristone in the treatment of the signs and symptoms of endogenous Cushing's syndrome. Total treatment duration may be up to 12 months or longer at the discretion of the Investigator.
• Detailed Description: Up to 50 subjects will receive mifepristone daily. Subjects completing 24 weeks of mifepristone treatment under Corcept protocol C1073-400 (NCT00569582) will be eligible to continue treatment for an additional 1 year. Assessments of safety, as evaluated by physical examinations, vital signs, laboratory tests and adverse events, will be made. Persistence of improvement in response to mifepristone treatment will also be evaluated during this extension study by assessing the continued or sustained improvement in the signs and symptoms of Cushing's syndrome.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cushing's Syndrome

Intervention

Drug: mifepristone

Mifepristone 300 mg to 1200 mg once daily

Other Name: CORLUX

Study Arms

Experimental: Mifepristone

Mifepristone 300mg to 1200mg once daily

Intervention: Drug: mifepristone

Publications *

• Fein HG, Vaughan TB 3rd, Kushner H, Cram D, Nguyen D. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC Endocr Disord. 2015 Oct 27;15:63. doi: 10.1186/s12902-015-0059-5.
• Fleseriu M, Findling JW, Koch CA, Schlaffer SM, Buchfelder M, Gross C. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27. doi: 10.1210/jc.2014-1843. Epub 2014 Jul 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2014): 30
• Original Estimated Enrollment (submitted: July 9, 2009): 50
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have completed the Week 24 visit and the 6-Week Follow-up visit of Corcept Study C-1073-400 (NCT00569582).
• In the opinion of the Investigator, are expected to maintain clinical benefit from mifepristone.
• Women of childbearing potential have a negative serum pregnancy test at Entry.
• Women of childbearing potential must be willing to use non-hormonal, medically acceptable methods of contraception during the study.
• Are able to provide written informed consent
• Are able to return to the investigative site to complete the study evaluations outlined in the protocol.
• Will not use systemic estrogens during the study.

Exclusion Criteria:

• Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.
• Are taking medications within 14 days of the Entry visit that a) have a large first pass metabolism that is largely mediated by CYP3A4 and which have a narrow therapeutic margin; and/or b) are strong CYP3A4 inhibitors.
• Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study.
• Have received investigational treatment (drug, biological agent or device) other than CORLUX (mifepristone) within 30 days of Entry
• Have a history of an allergic reaction or intolerance to CORLUX (mifepristone)
• Have uncorrected hypokalemia (potassium level of <3.5 mEq/L) at Entry. Spironolactone or eplerenone is allowed to control hypokalemia.
• Postmenopausal women with a history of endometrial hyperplasia with atypia or pathological features consistent with endometrial carcinoma.
• Thickened endometrium on the Entry Visit transvaginal ultrasound that has not resolved after induction of menstrual bleeding with progesterone.
• Uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
• Any woman with an intact uterus who has a hemorrhagic disorder or is being treated with an anticoagulant (e.g. warfarin, heparin).
• Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL.
• Elevated total bilirubin >1.5 ULN, elevated ALT or AST ≥3X the upper limit of normal.

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: United States

Administrative Information

• NCT Number: NCT00936741
• Other Study ID Numbers: C-1073-415
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Corcept Therapeutics
• Original Responsible Party: Coleman Gross, MD, Corcept Therapeutics
• Current Study Sponsor: Corcept Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Coleman Gross, MD; Corcept Therapeutics

• PRS Account: Corcept Therapeutics
• Verification Date: February 2014