A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome (SEISMIC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Corcept Therapeutics
ClinicalTrials.gov Identifier:
NCT00569582
First received: December 5, 2007
Last updated: August 12, 2013
Last verified: August 2013
  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 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Responder is defined as subject with a decrease greater than or equal to 25% in area under the curve for glucose on 2-hour oral glucose test from baseline to week 24 or last visit, for Cushing's patients with type-2 diabetes mellitus/impaired glucose tolerance.

  • Decrease in Diastolic Blood Pressure. [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Responder is defined as subject with a decrease greater than or equal to 5mm Hg in diastolic blood pressure from baseline to week 24 or last visit.


Enrollment: 50
Study Start Date: December 2007
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.
Other Name: CORLUX

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569582

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
The University of Chicago
Chicago, Illinois, United States, 60637
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 HSC
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 University Health Science 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
Diabetes and Glandular Disease Clinic
San Antonio, Texas, United States, 78229
United States, Wisconsin
Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin
Menomonee Falls, Wisconsin, United States, 53051
Sponsors and Collaborators
Corcept Therapeutics
Investigators
Study Director: Coleman Gross Corcept Therapeutics
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT00569582     History of Changes
Other Study ID Numbers: C-1073-400
Study First Received: December 5, 2007
Results First Received: April 4, 2012
Last Updated: August 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Corcept Therapeutics:
Cushing's Disease
Cushing's Syndrome
Cushings
Cushing Syndrome
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
Ectopic ACTH Secretion

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

ClinicalTrials.gov processed this record on October 22, 2014