Clinical trial NCT00936741: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cushing's Syndrome
Keywords: 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
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-07-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to three years.
Secondary outcomes:
measure: 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
timeFrame: Up to three years.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: Escondido
country: United States
facility: AMCR Institute Inc.
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Hollywood
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine
state: Illinois
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Diabetes Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Menomonee Falls
country: United States
facility: Endocrinology Center at Community Medical Commons
state: Wisconsin
Study officials:
affiliation: Corcept Therapeutics
name: Coleman Gross, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.