EUCTR2017-001219-35-IT进行中（未招募）1 期
A Double-blind, Placebo-Controlled, Randomized Withdrawal Following Open-label Therapy Study to Assess the Safety and Efficacy of Levoketoconazole (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
- 35
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
- 性别
- All
入选标准
- •Inclusion Criteria for Specified Subjects Completing the SONICS Study:
- •SONICS-completers, including those receiving open-label treatment after SONICS as part
- •of an Expanded Access Program (EAP) or OLE study, whose completion of the M12 visit
- •occurred not more than 6 months prior to the anticipated Randomization Visit (RW0), may
- •be eligible for the study if the following two inclusion criteria are met:
- •1. Completed the final SONICS visit (M12) and have demonstrated maintenance of clinical
- •response (partial or complete) on a stable Therapeutic Dose of levoketoconazole for at
- •least 12 weeks prior to study entry (Visit RW0)
- •2. Able and willing 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
- •Inclusion Criteria for All Others:
- •The following categories of potential subjects, categorized by prior use of
- •levoketoconazole, may be eligible if the following 11 inclusion criteria are all met:
- •Naïve to levoketoconazole (defined as having never participated in SONICS);
- •Completers of SONICS visit M12 more than 6 months prior to the expected RW0 visit of
- •the current study;
- •Completers of SONICS visit M12 within the 6 months prior to the expected RW0 visit who
- •have not been receiving a stable Therapeutic Dose of levoketoconazole for at least 12
- •weeks prior to the start of screening.
- •1. Male or female and at least 18 years of age.
- •2. Able and willing to provide written informed consent
- •3. Confirmed newly diagnosed, persistent or recurrent endogenous Cushing’s syndrome of
- •any etiology, except secondary to malignancy (including pituitary or adrenal carcinoma).
- •Persistence will not be considered confirmed until 6 weeks or more post-surgery
- •4. Elevated mean 24 hour UFC levels at least 1.5X ULN of the normative range of the
- •study’s central laboratory assay and from a minimum of three measurements from
- •adequately collected urine; the study’s central laboratory must be used for all
- •qualifying measurements.
- •5. Presence of abnormal values from at least one of these two diagnostic tests
- •(discrepancies between test findings will not be investigated nor considered
- •exclusionary):
- •Abnormal Dexamethasone Suppression Test (DST): Elevated 8 AM blood cortisol at least
- •1.8 µg/dL (50 nmol/L) after 1 mg dexamethasone orally at 11 PM the evening prior with
- •concurrent dexamethasone blood concentration greater than 5.6 nmol/liter (220 ng/dL)
- •(results from within the 2 months prior to start of Screening or newly tested with
- •results available by the Baseline Visit [TM0]) OR
- •Elevated LNSC concentrations (at least two measurements) each greater than the ULN of
- •the study’s central laboratory normative range; the study’s test kit and lab must be
- •used for all qualifying measurements.
- •6. Non-candidates for CS-specific surgery, refuse surgery or surgery will be delayed
- •until after study completion and agree to complete this study prior to surgery.
- •7. If post-surgical for CS-specific surgery, then no significant post operative sequelae
- •remain and the risk of such sequelae is considered negligible.
- •8. Agree to the following minimum washout periods prior to the Baseline Visit (TM0) (as
- •applicable):
- •Ketoconazole or metyrapone: 2 weeks;
- •Dopamine agonists: bromocriptine (2 weeks), cabergoline (8 weeks);
- •Octreotide acetate LAR, lanreotide Autogel®, pasireotide LAR: 12 weeks;
- •Lanreotide SR: 8 weeks;
- 另有 1 项未显示
排除标准
- •Subjects will be excluded from the study if ANY of the following criteria are met (NOTE:
- •exclusion criteria apply to and must be assessed in both cohorts):
- •1. Enrolled in SONICS but have not completed SONICS through Visit M12
- •2. Pseudo-Cushing’s syndrome based on assessment of the Investigator
- •3. Cyclic Cushing’s syndrome with multi-week periods of apparent spontaneous CS
- •4. Non-endogenous source of hypercortisolism, including pharmacological
- •corticosteroids or ACTH
- •5. Radiotherapy of any modality directed against the source of hypercortisolism within
- •the last 5 years
- •6. Treatment with mitotane within 6 months of enrollment
- •7. History of malignancy, including adrenal or pituitary carcinomas (other than low
- •risk, well-differentiated carcinomas of thyroid, breast or prostate that are very
- •unlikely to require further treatment in the opinion of the treating physician, or
- •squamous cell or basal cell carcinoma of the skin)
- •8. Clinical or radiological signs of compression of the optic chiasm
- •9. Major surgery within 1 month of Screening (or within 6 weeks for pituitary surgery)
- •10. Clinically significant abnormality in 12-lead ECG during the Screening Phase
- •requiring medical intervention
- •11. QTc interval above 470 msec during the Screening Phase
- •12. History of Torsades des Pointes, ventricular tachycardia, ventricular fibrillation,
- •history of prolonged QT syndrome
- •13. Use of medications associated with possible, probable, or definite QT/QTc
- •prolongation
- •14. Pre-existing hepatic disease
- •15. Hepatitis B surface antigen (HbsAg) or hepatitis C-positive
- •16. Human immunodeficiency virus (HIV)-positive.
- •17. History of symptomatic cholelithiasis with intact gallbladder
- •18. History of pancreatitis
- •19. Liver safety tests during the Screening Phase as follows:
- •- ALT and/or AST above 3X ULN
- •- Alkaline phosphatase or TBN above 2X ULN
- •Subjects with isolated indirect TBN up to 3X ULN are presumed to have Gilbert’s syndrome
- •and may be enrolled if all other liver safety tests are within normal levels
- •20. History of documented or suspected drug-induced liver injury to ketoconazole or any
- •other azole drug
- •21. Serum potassium below 3.0 mEq/L
- •22 Abnormal free thyroxine (FT4), unless subsequently corrected and stable for at least
- •4 weeks. Subjects with thyroid-stimulating hormone (TSH) less than the lower limit of
- •normal (LLN) and normal FT4 are potentially eligible without intervention
- •23. History of persistent uncontrolled hypertension
- •24. Hypercholesterolemia currently treated with atorvastatin, lovastatin or simvastatin
- •and unwilling or unable to change to alternative therapy with: pravastatin, fluvastatin,
- •pitavastatin or rosuvastatin (must switch statin at least 2 weeks prior to dosing) or
- •another allowed therapy. For
- •25. More than one hospitalization for hyperglycemia or complication of diabetes during
- •the last 12 months
- •26. Decreased renal function as defined by eGFR below 40 mL/min/1.73 m2, using MDRD
- •equation for eGFR
- •27. Pregnant or lactating
- •28. Body habitus preventing repeated venipuncture as required by protocol
- 另有 6 项未显示
研究者
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