A clinical study to find out whether a new drug known as COR-003 is safe and effective in people who have Cushing’s Syndrome
- Conditions
- MedDRA version: 17.0 Level: LLT Classification code 10011657 Term: Cushings syndrome System Organ Class: 100000004860Endogenous Cushing's syndrome (CS)Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2013-002133-37-IT
- Lead Sponsor
- Cortendo AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 90
Subjects eligible for enrollment in the study must meet all the following criteria:
1. Male or female =18 years of age
2. Confirmed diagnosis of persistent or recurrent CS (with or without therapy) or newly diagnosed disease, if they are not candidates for surgery. CS will be defined according to the criteria in the guidelines for diagnosis of CS (Nieman 2008).Previous medical records will be collected and used to support the diagnosis. The diagnostic criteria for appropriateness of inclusion of each subject into the study will be reviewed by the Medical Monitor.
3. Previously irradiated subjects will be allowed as long as the radiation treatment occurred > 4 years ago and they have not exhibited evidence for improvement in their underlying Cushing’s disease for 6 months. The total number of previously irradiated subjects enrolled in this study will not exceed 10.
In the vast majority of subjects treated with radiation, efficacy is observed in
<4 years.
4. Subjects who refuse surgery or in whom surgery will be delayed beyond the projected duration of this study will be permitted to participate.
5. Confirmed diagnosis of persistent or recurrent endogenous hypercortisolemia as defined by elevated 24-hour UFC levels on repeated determinations (described in Inclusion #2) caused by either ACTH-dependent or ACTH-independent etiologies.
• Cushing’s Disease (CD) which is specifically defined as mean 24-hour UFC
level of =1.5X ULN on repeated determination, morning plasma
corticotropin (ACTH) level of 5 ng/L (1.1 nmol /L) or more, a confirmed
pituitary source of CD (documentation of ACTH immunoreactivity on
pathological evaluation), and as determined by medical records (including
surgical reports and pituitary imaging scans), or bilateral inferior petrosal
sinus sampling (BIPSS) with a central to peripheral ratio of >2 before or >3
after corticotropin-releasing hormone (CRH) administration)
• Ectopic ACTH secretion, not of pituitary origin
• Ectopic CRH secretion
• Adrenal-dependent CS (adrenal adenoma, adrenal autonomy)
• Etiology unknown
6. Subjects whose CS is due to Cushing’s disease without adenomas based on a pituitary magnetic resonance imaging (MRI) scan may be enrolled as long as biochemical criteria in Inclusion Criteria #5 are met.
7. Subjects on treatment for CS for whom treatment has been inadequate or not well tolerated must agree to the following minimum washout periods as determined by the nature of their treatment before baseline assessments are performed for participation
in this study:
• Inhibitors of steroidogenesis: 2 weeks
• Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks)
• Octreotide acetate LAR and lanreotide Autogel®: 12 weeks
• Lanreotide SR/long-acting pasireotide: 8 weeks
• Octreotide acetate (immediate release formulation) or short-acting pasireotide:
1 week
• Mifepristone (RU 486): 4 weeks
• Mitotane: >6 months and have serum concentrations <5 µg/mL
8. Subjects on
Subjects will be excluded from the study if any of the following criteria are met:
1. De novo Cushing´s disease AND a candidate for pituitary surgery
• If surgery is to be delayed for >6 months, subjects may be allowed to participate in the trial while awaiting surgery, but must agree to complete this study prior to surgery.
2. Subjects treated with radiation within the previous 4 years.
• In the vast majority of subjects treated with radiation, efficacy is observed in <4 years .
3. Subjects who have been treated with mitotane within 6 months of screening or have levels exceeding 5 µg/mL.
4. Pseudo-Cushing’s syndrome based on clinical assessment of the investigator.
5. Subjects with adrenal carcinoma
6. Body habitus preventing repeated venipuncture as required by protocol
7. Subject is currently in another study or has received any investigational treatment (drug, biological agent or device) within 30 days or 5 half lives of screening, whichever is longer
8. History of documented clinically significant liver function abnormalities requiring drug discontinuation on ketoconazole or closely related chemical analogues (for example, itraconazole).
9. Male and female subjects with QTc interval of >470 msec
10. History of Torsades des Pointes or ventricular tachycardia or ventricular fibrillation or history of prolonged QT syndrome (including family history) or use of medications resulting in QT/QTc prolongation or hypokalemia <3.0 meq/L
11. Subjects with a non-endogenous source of hypercortisolemia such as exogenous source of glucocorticoids or therapeutic use of ACTH
12. History of malignancy, other than thyroid, early stage prostate, squamous cell and basal cell carcinoma, within 3 years prior to the initial dose of the study medication. Subjects with history of carcinoma must have a life expectancy of >1 year and must be on stable doses of their specific therapies. Subjects with early stage prostate cancer undergoing no treatment due to low grade potential may be enrolled.
13. Diagnosis of HIV
14. History of persistent uncontrolled hypertension (> 180/120 mmHg) despite medical intervention
15. Subjects with hypercholesterolemia who are on current atorvastatin or simvistatin and not willing or unable to change to alternative therapies as noted (pravastatin, fluvastatin, and rosuvastatin) with 2 weeks of study screening
16. Subjects with Type 2 Diabetes Mellitus (T2DM) or with a history of hyperglycemic episodes requiring repeated, frequent hospitalizations specifically for diabetic management
17. Subjects with decreased renal function as defined by eGFR =40 mL/min/1.73 m2, using Modified Diet in Renal Disease (MDRD) equation for estimating renal function (eGFR).
18. Any other clinically significant medical condition, as determined by the Investigator that precludes enrollment and participation in the study through completion (for example, New York Heart Association (NYHA) class III or IV congestive heart failure).
19. Known hepatic disease, other than mild to moderate hepatic steatosis consistent with fatty infiltration (non-alcoholic steatohepatitis [NASH]), with on
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method