Cushing's Syndrome
Conditions
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
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.
Interventions
DRUGmifepristone
Mifepristone 300 mg to 1200 mg once daily
Sponsors
Corcept Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to three years. | Subjects who received at least one dose of mifepristone were included in the safety analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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). |
Countries
United States
Participant flow
Recruitment details
Subjects completing 24 weeks of mifepristone treatment under Corcept protocol C1073-400 (NCT00569582) were eligible to continue treatment in C1073-415 at the dose being administered at the end of treatment in C1073-400 (NCT00569582).
Pre-assignment details
Only subjects who had completed C1073-400 (NCT00569582) were enrolled. All subjects received active drug (no placebo).
Participants by arm
| Arm | Count |
|---|---|
| Open-label mifepristone at doses from 300 mg/day up to 1200 mg/day daily | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Open-label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 46.1 years STANDARD_DEVIATION 11.74 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 18 / 30 |
Outcome results
Primary
Number of Participants With Adverse Events
Subjects who received at least one dose of mifepristone were included in the safety analysis.
Time frame: Up to three years.
Population: Subjects who received one dose of study drug were included in the safety and ITT analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label | Number of Participants With Adverse Events | 30 participants |
Secondary
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
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).
Time frame: Up to three years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label | 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 | 3.3 units on a scale | Standard Deviation 1.74 |