EUCTR2013-002133-37-CZ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
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 if subjects are not candidates for surgery or radiotherapy CD is defined according to the criteria in the Endocrine Society Clinical Practice Guideline for diagnosis of CD (Nieman 2008). Previous medical records will be collected and used to support the diagnosis of CD.Specifically, CD is 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
- •Either MRI confirmation of pituitary macroadenoma, or inferior petrosal sinus
- •gradient >3 after corticotropin-releasing hormone (CRH) stimulation for those
- •patients with a microadenoma, or for subjects who have had prior pituitary
- •surgery, histopathology confirming and ACTH-staining adenoma. If inferior
- •petrosal sampling had been performed without CRH, then a central to peripheral
- •pre-stimulation gradient >2 is required
- •4. Confirmed diagnosis of newly diagnosed, persistent or recurrent endogenous CS of other etiology if subjects are not candidates for surgery or radiotherapy. CS will be defined according to the criteria in the Endocrine Society Clinical Practice Guideline for diagnosis of CS (Nieman 2008). Previous medical records will be collected and used to support the diagnosis, and the differentiation of the cause of CS, specifically
- •Mean 24-hour UFC level of =1.5X ULN on repeated determination
- •Ectopic ACTH secretion, not of pituitary origin
- •Ectopic CRH secretion
- •Adrenal-dependent CS (adrenal adenoma, adrenal autonomy)
- •Etiology unknown
- •5. Subjects MUST have elevated mean 24-hour UFC levels =1.5X ULN of assay based on a minimum of four measurements from adequately collected urine. Urine may be collected on sequential days.
- •6. 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 previous 2 months before start of Screening Phase; in that case previous test results and details of conduct will need to be available by the Baseline visit)
- •Elevated late night salivary cortisol concentrations (at least two measurements)
- •7. Previously irradiated subjects with CD or CS of other etiology will be allowed as long as the radiation treatment occurred > 4 years ago and subjects 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.
- •8. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse surgery, or in whom surgery will 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. For subjects who have already undergone surgery, a minimum of 3 months sh
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 >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.
- •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 >2 X ULN
- •If all LFTs are within normal limits and total bilirubin 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 with pravastatin, fluvastatin, and 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 5 half-lives of treatment, whichever is longer.
- •23. Repeated hospitalization for
研究者
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