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 or Cushing's Disease
- Conditions
- Endogenous Cushing's syndrome (CS) or Cushing's diseaseMedDRA version: 19.1 Level: LLT Classification code 10011657 Term: Cushings syndrome System Organ Class: 100000004860Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2013-002133-37-BG
- Lead Sponsor
- Cortendo AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 90
1. Male or female =18 years of age
2. Able to provide written informed consent prior to any study
procedures being performed; eligible subjects must be able to
understand the informed consent form prior to inclusion into the study.
3. Confirmed diagnosis of newly diagnosed, persistent or recurrent CD or endogenous CS of other etiology if subjects are not candidates for surgery or radiotherapy within the 18 months after enrollment.
Previous medical records will be collected and used to support the
diagnosis of CD or endogenous CS of other etiology, including the
following etiologies:
• Ectopic ACTH secretion, i.e. ACTH not of pituitary origin
• Ectopic corticotropin-releasing hormone (CRH) secretion
• Adrenal-dependent CS (i.e. adrenal adenoma (NOT carcinoma), adrenal hyperplasia, etc.)
• Etiology unknown
In the absence of pathological or post-surgical confirmation of the
diagnosis of CD (i.e. documented adrenal insufficiency postadenomectomy or hypophysectomy, which will be considered
diagnostic). The following historical evidence will be considered
satisfactory to establish the diagnosis of CD:
• Plasma corticotropin (ACTH) level >20 pg/mL (4.5 pmol/L) or greater (Note: ACTH =5 pg/mL (1.1 pmol/L) and =20 pg/mL will generally suffice only if accompanied by either a positive CRH stimulation test or DST or combined CRH-DST) PLUS one of the diagnostic strategies described below based on pituitary MRI/computed tomography (CT) findings (Note: pituitary imaging preceding the original diagnosis is a requirement for eligibility):
• For tumors =6 mm by imaging:
- Inferior petrosal sinus sampled (IPSS) ACTH central:plasma gradient
=2 before CRH or =3 after CRH, OR if IPSS was not done then:
- Positive ACTH and/or cortisol response to CRH/desmopressin or
combined CRH-desmopressin stimulation plus high-dose (8 mg)
dexamethasone suppression of plasma cortisol, ideally on more than one occasion, performed and interpreted according to internationally
recognized standards of diagnosis
- In the absence of IPPS and the combination of tests described, an
individual might be eligible if CD was otherwise confirmed via adequate testing. Such cases must be discussed with and explicitly approved by the Medical Monitor, and the specific diagnostic criteria used to establish the diagnosis of CD must be documented.
• For tumors <6 mm or not visible by MRI:
- IPSS with ACTH central:plasma gradient =2 before CRH or =3 after
CRH
- In the absence of IPSS, an individual might be eligible if CD was
otherwise confirmed via adequate testing. Such cases must be discussed with and explicitly approved by the Medical Monitor, and the specific diagnostic criteria used to establish the diagnosis of CD must be documented.
4. Regardless of the etiology of endogenous CS, subjects MUST have
elevated mean 24-hour UFC levels =1.5X ULN based on the normative range of the central lab assay and on a minimum of four measurements from adequately collected urine. Urine
1. Subjects with Pseudo-CS based on assessment of the Investigator
2. Subjects with cyclic CS based on assessment of the investigator
3. Subjects with a non-endogenous source of hypercortisolism such as exogenous source of glucocorticoids or therapeutic use of ACTH.
4. Known inherited syndrome as the cause of hypercortisolism, including but not limited to multiple endocrine neoplasia Type 1, McCune Albright Syndrome and Carney Complex
5. Subjects with adrenal carcinoma
6. History of malignancy, other than thyroid, early stage prostate,
squamous cell and basal cell carcinoma, within 3 years prior to the
Screening Phase. Subjects with history of such allowed carcinoma must have a life expectancy of >18 months and must be considered medically stable. Subjects with early stage prostate cancer undergoing no treatment due to low grade potential may be enrolled
7. Clinical or radiological signs of compression of the optic chiasm
8. Major surgery within 1 month prior to enrollment
9. Subjects with clinically significant abnormality in 12-lead ECGs during the Screening Phase needing medical intervention
10. Subjects with QTc interval of >470 msec during the Screening Phase
11. Subjects with a 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.
12.Pre-existing hepatic disease; subjects with mild to moderate hepatic steatosis consistent with fatty infiltration (non-alcoholic fatty liver disease [NAFLD] are allowed)
13. Positive for HbsAg or positive HBC test.
14. History or symptoms of recurrent symptomatic cholelithiasis or
pancreatitis
15. LFT must not be above the following cut-offs during the Screening
Phase:
• ALT and/or AST >3 X ULN
• Total bilirubin (TBN) >2 X ULN
If all LFTs are within normal limits and TBN is elevated, examination of direct and indirect bilirubin may be conducted. Subjects with isolated indirect TBN up to 3X ULN are presumed to have Gilbert's syndrome and may be enrolled if all other LFTs are within normal levels
16. History of documented or suspected drug-induced liver injury
requiring drug discontinuation of ketoconazole or any azole antifungals
17. Pregnant or lactating women
18. HIV positive
19. History of persistent uncontrolled hypertension (>180/120 mmHg) despite medical intervention.
20. Subjects with hypercholesterolemia currently treated with
atorvastatin, lovastatin or simvastatin and not willing or unable to
change to alternative therapies i.e. pravastatin, fluvastatin, or
rosuvastatin within 2 weeks of start of the Screening Phase.
21. Body habitus preventing repeated venipuncture as required by
protocol.
22. Subject is currently in another study or has received any
investigational treatment (drug, biological agent or device) within 30
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