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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cushing's Syndrome	Drug: mifepristone	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: July 2009
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Mifepristone; Mifepristone 300mg to 1200mg once daily	Drug: mifepristone; Mifepristone 300 mg to 1200 mg once daily; Other Name: CORLUX

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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)".

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States, 35294

United States, California

AMCR Institute Inc.

Escondido, California, United States, 92026

Stanford University Medical Center

Stanford, California, United States, 94305-5826

United States, Florida

The Center for Diabetes and Endocrine Care

Hollywood, Florida, United States, 33021

United States, Illinois

Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine

Chicago, Illinois, United States, 60611

United States, Maryland

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21215

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

University of Michigan Medical Center

Ann Arbor, Michigan, United States, 48109

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87131

United States, Ohio

Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism

Cleveland, Ohio, United States, 44195

United States, Oklahoma

Oklahoma Diabetes Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Oregon Health Sciences University

Portland, Oregon, United States, 97239

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390-8857

United States, Wisconsin

Endocrinology Center at Community Medical Commons

Menomonee Falls, Wisconsin, United States, 53051

Sponsors and Collaborators

Corcept Therapeutics

Investigators

• Study Director: Coleman Gross, MD; Corcept Therapeutics

More Information

Additional Information:

Corcept C-1073-400 Clinicaltrials.gov Study Listing 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Corcept Therapeutics
• ClinicalTrials.gov Identifier: NCT00936741
• Other Study ID Numbers: C-1073-415
• First Posted: July 10, 2009
• Results First Posted: April 2, 2014
• Last Update Posted: April 2, 2014
• Last Verified: February 2014

Keywords provided by Corcept Therapeutics:

Cushing's Disease; Cushing's Syndrome; Cushings; Pituitary; ACTH; Adrenocorticotropic hormone; Ectopic; Adrenal adenoma; Adrenal carcinoma; Adrenal autonomy; Cortisol; Hypercortisolemia; Cushingoid; Moon facies; Dorsocervical fat; Plethora; Hirsutism; Violaceous striae; Hormone; Contraceptive; Endocrine; Cushing Syndrome; Ectopic ACTH Secretion

Additional relevant MeSH terms:

Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Mifepristone; Abortifacient Agents, Steroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Hormonal; Menstruation-Inducing Agents