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A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome (SEISMIC)
This study is currently recruiting participants.
Verified by Corcept Therapeutics, December 2009
First Received: December 5, 2007   Last Updated: December 21, 2009   History of Changes
Sponsor: Corcept Therapeutics
Information provided by: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT00569582
  Purpose

Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.


Condition Intervention Phase
Cushing's Syndrome
Drug: mifepristone
Phase III

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: An Open-label Study of the Efficacy and Safety of CORLUX (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome

Resource links provided by NLM:


Further study details as provided by Corcept Therapeutics:

Primary Outcome Measures:
  • Improvement in diabetes and/or glucose intolerance and/or hypertension and; drug safety. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Improvement in other symptoms of Cushing's Syndrome. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2007
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: mifepristone
Patients take mifepristone by mouth once a day. The dose is increased during scheduled timepoints during the study or until symptoms improve or the highest dosage allowed is reached. Dose escalation will be based upon weight. During clinic visits, blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis will be performed.

Detailed Description:

Cushing's syndrome is a relatively rare disorder caused by prolonged exposure to high levels of the glucocorticoid hormone cortisol. Cushing's syndrome may result from elevated endogenous or exogenous sources of cortisol. Endogenous Cushing's syndrome resulting from cortisol overproduction by the adrenal glands is the subject of this protocol. Patients with exogenous Cushing's syndrome, which develops as a side effect of chronic administration of high doses of glucocorticoids, are not eligible for enrollment in this study.

This will evaluate the safety and efficacy of mifepristone for treatment of the signs and symptoms of hypercortisolemia in patients with endogenous Cushing's syndrome from ACTH-dependent or adrenal disorders.

The study will enroll subjects for whom the investigator has determined that medical treatment of endogenous hypercortisolemia is needed. Medical treatment may be intended to treat the effects of persistent or recurrent hypercortisolemia after surgery and/or radiation for Cushing's syndrome, to bridge the period of time for radiation to become effective, or when surgery is not feasible.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Individuals eligible for enrollment into this study are adult male and non-pregnant female adult patients who:

  • Are at least 18 years of age
  • Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or ACTH independent etiologies, including

    1. Cushing's Disease (that has recurred after primary pituitary surgery, or has failed pituitary surgery, or has been treated with radiation therapy to the pituitary, or is not treatable with surgery, or exists in patients who are not candidates for surgery, and is confirmed by documentation of ACTH immuno-reactivity on a pathological evaluation of pituitary tissue from a previous surgical specimen or IPSS with a central-to-peripheral gradient (ratio) of >2 before or >3 after CRH administration).
    2. Ectopic ACTH
    3. Ectopic CRF secretion
    4. Adrenal adenoma
    5. Adrenal carcinoma
    6. Adrenal autonomy
  • Require medical treatment of hypercortisolemia
  • Have diabetes mellitus type 2 or glucose intolerance AND/OR have hypertension *Note: To be eligible for inclusion subjects must have documented evidence of persistent endogenous hypercortisolemia

Exclusion Criteria:

Individuals not eligible to be enrolled into the study are those who:

  • Have de novo Cushing's disease and are surgical candidates for pituitary surgery.
  • Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.
  • Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism largely mediated by CYP3A4 and 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) within 30 days of Screening
  • Have a history of an allergic reaction or intolerance to CORLUX (mifepristone)
  • Have a non-endogenous source of hypercortisolemia such as factious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing's syndrome), factious or therapeutic use of ACTH
  • Have Pseudo-Cushing's syndrome.
  • Receive PPARgamma agonist drugs (e.g. pioglitazone, rosiglitazone) within 4 months of Baseline (Day 1).
  • Postmenopausal women with an intact uterus who have experienced unexplained vaginal bleeding within 12 months of Screening are excluded.
  • Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00569582

Contacts
Contact: Chris Ward, Sponsor Contact 650-688-8807 cward@corcept.com

  Show 21 Study Locations
Sponsors and Collaborators
Corcept Therapeutics
Investigators
Study Director: Coleman Gross Corcept Therapeutics
  More Information

Additional Information:
Publications:
Responsible Party: Corcept Therapeutics ( Coleman Gross )
Study ID Numbers: C-1073-400
Study First Received: December 5, 2007
Last Updated: December 21, 2009
ClinicalTrials.gov Identifier: NCT00569582     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Corcept Therapeutics:
Pituitary
Cushing's Disease
Cushing's Syndrome
Cushings
ACTH
Adrenocorticotropic hormone
Ectopic
Adrenal adenoma
Adrenal carcinoma
Adrenal autonomy
Cortisol
Hypercortisolemia
Cushinoid
Moon facies
Dorsalcervical fat
Plethora
Hirsutism
Violaceous striae
Hormone
Contraceptive
Endocrine
Cushing Syndrome
Cushing's Disease
Cortisol
Ectopic ACTH Secretion

Additional relevant MeSH terms:
Contraceptives, Postcoital, Synthetic
Contraceptive Agents
Hormone Antagonists
Physiological Effects of Drugs
Contraceptives, Oral
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Adrenal Gland Diseases
Reproductive Control Agents
Hormones
Adrenocortical Hyperfunction
Adrenocorticotropic Hormone
Pathologic Processes
Syndrome
Therapeutic Uses
Abortifacient Agents
Menstruation-Inducing Agents
Contraceptives, Oral, Synthetic
Abortifacient Agents, Steroidal
Disease
Cushing Syndrome
Endocrine System Diseases
Mifepristone
Contraceptives, Postcoital
Luteolytic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010