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

August 12, 2013 updated by: Corcept Therapeutics

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham School of Medicine
    • California
      • Escondido, California, United States, 92026
        • AMCR Institute Inc.
      • Stanford, California, United States, 94305-5826
        • Stanford University Medical Center
    • Florida
      • Hollywood, Florida, United States, 33021
        • The Center for Diabetes and Endocrine Care
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico HSC
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Health Science Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health Sciences University
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • San Antonio, Texas, United States, 78229
        • Diabetes and Glandular Disease Clinic
    • Wisconsin
      • Menomonee Falls, Wisconsin, United States, 53051
        • Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • CORLUX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in Diabetes and/or Glucose Intolerance.
Time Frame: Baseline to Week 24
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.
Baseline to Week 24
Decrease in Diastolic Blood Pressure.
Time Frame: Baseline to Week 24
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.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corcept Therapeutics

Investigators

  • Study Director: Coleman Gross, Corcept Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

December 5, 2007

First Submitted That Met QC Criteria

December 6, 2007

First Posted (Estimate)

December 7, 2007

Study Record Updates

Last Update Posted (Estimate)

August 22, 2013

Last Update Submitted That Met QC Criteria

August 12, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-1073-400

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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