EUCTR2017-001219-35-PL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
- 54
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 SONICS-Completers:
- •Subjects who have completed the SONICS study, within 6 months of the screening visit, including those receiving open-label treatment after SONICS as part of an EAP 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 of the screening visit of the current study;
- •Completers of SONICS visit M12 within 6 months of the screening 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.
- •NOTE: This criterion does not apply to subjects currently on levoketoconazole.
- •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 mcg/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.
- •NOTE: Abnormal LNSC is required among eligible subjects with estimated glomerular filtration rate (eGFR as determined by Modified Diet in Renal Disease MDRD equation) above 40 and below 60 mL/min/1.73 m2 .
- •NOTE: This criterion does not apply to subjects currently on levoketoconazole.
- •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 a
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 not completed SONICS through Visit M12
- •2.Pseudo-Cushing’s syndrome based on Investigator assessment
- •3.Cyclic Cushing’s syndrome with multi-week periods of apparent spontaneous CS remission
- •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 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 via central reader interpretation
- •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 total bilirubin above 2X ULN Subjects with isolated indirect bilirubin up to 3X ULN are presumed to have Gilbert’s syndrome & may be enrolled if all other liver 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 4.0 mEq/L
- •22.Abnormal FT4, unless subsequently corrected and stable for at least 4 weeks. Subjects with TSH less than the 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 subjects for whom lipid reduction therapy is considered, drugs should be added and stabilized for at least 4 weeks prior to TM0 for the levoketoconazole-naïve cohort or RW0 for the SONICS-completers cohort, as improvements in lipids are being assessed as an endpoint for levoketoconazole treatment
- •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
- •29.Any other clinically significant medical condition, as determined by the Investigator that precludes enrollment and participation in the study through completion, including
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