EUCTR2013-002133-37-SE进行中（未招募）1 期
An Open Label Study to Assess the Safety and Efficacy of COR—003 (2S, 4R-Ketoconazole) in the Treatment of Endogenous Cushing’s Syndrome
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Cortendo AB
- 入组人数
- 90
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
入选标准
- •1. Male or female =18 years of age
- •2. Able to provide written informed consent.
- •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 post- adenomectomy 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 will ideally be collected on sequential days.
- •5. In addition to elevated mean UFC, presence of abnormal values from one of the following tests:
- •Abnormal DST: Elevated 8 AM serum cortisol =1.8 µg/dL (50 nmol/L) after 1 mg dexamethasone orally at 11 PM the evening prior (if not conducted already in the diagnostic workup of the subject within the prev
排除标准
- •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. Preexisting 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
- •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 who are 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 days or five half-lives of treatment, whichever is longer
- •23. Repeated hospitalization for hyperglycemia or for any complication of hyperglycemia an
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