2025-524649-28-00招募中4 期
A double-blind, randomised, 30-week placebo-controlled phase IV study to assess the efficacy and safety of osilodrostat in patients with hypertension caused by hypercortisolaemia due to Cushing’s Syndrome
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Recordati AG
- 入组人数
- 51
- 试验地点
- 37
- 主要终点
- Normalization status for each participant at Week 30 of treatment with osilodrostat or placebo, based on the mean of UFC concentrations from two 24hour urine collections, with normalization defined as ≤1× the upper limit of normal (ULN).
研究概览
简要总结
To evaluate the efficacy of osilodrostat in terms of normalization of urinary-free cortisol (UFC)
研究设计
- 分配方式
- Randomized
- 主要目的
- Follow-up Phase (4 weeks)
- 盲法
- Double (Investigator, Monitor, Analyst, Subject, Carer)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 18 years of age
- •Able to provide and have provided signed written informed consent prior to study participation
- •Diagnosis of endogenous Cushing’s Syndrome
- •mUFC value from two 24h urinary collections > ULN and ≤ 2x ULN (individual UFCs may fall outside this range)
- •Participants with uncontrolled hypertension on stable doses of BP lowering medications (for at least 4 weeks); qualifying BP measurements by ABPM taken prior to randomisation defined as: Average of 24h ABPM SBP ≥ 135 mmHg and ≤ 170 mmHg or DBP ≥ 85 mmHg and ≤ 110 mmHg.
- •Participants under glucocorticoid replacement therapy can be recruited only if this therapy has been already stopped for at least seven days or 5 half-lives prior to screening, whichever was longer
- •Not taking any drug therapy for CS. The following minimum periods without these medications need to be completed before screening assessments: a. Steroidogenesis inhibitors (e.g. ketoconazole, metyrapone): 1 week b. Mifepristone: 3 weeks c. SC Pasireotide: 1 week d. Pasireotide LAR: 3 months e. Cabergoline: 4 weeks
- •Able to take oral medication and be willing to comply with the requirements of the study
排除标准
- •Previously treated with osilodrostat less than 12 weeks prior to start of screening
- •Pituitary radiation therapy within 3 years of screening
- •Ectopic ACTH syndrome or adrenocortical carcinoma with a life expectancy of <3 years or receiving chemotherapy
- •Having received prior mitotane treatment
- •Participants who are shift workers or have conditions that can affect the measurement of late-night salivary cortisol (LNSC) or the LDDST
- •Poorly controlled diabetes mellitus with a baseline HbA1c > 10.5%. Participants receiving glucose lowering medications must be on stable doses for at least 4 weeks prior screening.
- •Participants who are hypothyroid and not on adequate replacement therapy
- •History of major surgery/surgical therapy for any cause within 4 weeks before entering the study. Participants should have recovered from the surgery and be in good clinical condition before entering the study
- •Presence of bradycardia and/or QT-related exclusion criteria.
- •Total bilirubin > 1.5 x ULN and ALT or AST > 3 x ULN
- •Participation in any clinical investigation within 4 weeks prior to screening or longer if required by local regulation (Use of an investigational drug within 4 weeks prior to dosing)
- •Known hypersensitivity to osilodrostat
- •Occurrence of any significant acute illness within 3 weeks prior to dosing/randomisation
- •Female participants who are pregnant, intending to become pregnant or breastfeed during the study or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
- •Women of childbearing potential (WOCBP) who are unwilling to use highly effective contraception methods (Section 11.3)
- •Potentially unreliable or vulnerable participants (e.g. person kept in detention) and those judged by the Investigator to be unsuitable for the study
- •Presence of any severe and/or uncontrolled medical condition or other conditions that could affect participation in the study
- •Participants who are scheduled for a surgery to treat CS within 32 weeks of randomisation to the study drug
- •Presence of a known “long term” history of both hypertension and diabetes (defined as both hypertension and diabetes diagnosed >10 years prior to the initial diagnosis of endogenous CS)
- •History of cyclic Cushing’s Syndrome with fluctuating clinical manifestations
- •Participants with pseudo-CS
- •Participants with compression of the optic chiasm due to a macroadenoma or participants at high risk of compression of the optic chiasm (tumour within 2 mm of optic chiasm)
- •Participants who have undergone pituitary or adrenal surgery for Cushing’s syndrome within 3 months prior to screening.
研究组 & 干预措施
Decadron “0,5 mg Compresse” 10, 20 o 30 compresse
Auxiliary
干预措施: Decadron “0,5 mg Compresse” 10, 20 o 30 compresse (Drug)
null, null
Placebo
干预措施: null, null (Drug)
GLUCOSE
Auxiliary
干预措施: GLUCOSE (Drug)
Isturisa 1 mg film-coated tablets, Isturisa 5 mg film-coated tablets
Test
干预措施: Isturisa 1 mg film-coated tablets (Drug)
Isturisa 1 mg film-coated tablets, Isturisa 5 mg film-coated tablets
Test
干预措施: Isturisa 5 mg film-coated tablets (Drug)
结局指标
主要结局
Normalization status for each participant at Week 30 of treatment with osilodrostat or placebo, based on the mean of UFC concentrations from two 24hour urine collections, with normalization defined as ≤1× the upper limit of normal (ULN).
Normalization status for each participant at Week 30 of treatment with osilodrostat or placebo, based on the mean of UFC concentrations from two 24hour urine collections, with normalization defined as ≤1× the upper limit of normal (ULN).
次要结局
- Endpoint for key secondary objective: BP responder status for each participant (response is defined as ≥5 mmHg reduction in mean SBP and/or DBP as measured by ABPM, without worsening of either and without any modification in antihypertensive medications attributable to worsening hypertension) as measured at 30 weeks of treatment with osilodrostat or placebo.
- Endpoints for secondary objectives: 1. Frequencies and percentages of hypocortisolism-related AEs with osilodrostat or placebo including the following categories: a. Overall hypocortisolism-related AEs b. Glucocorticoid withdrawal syndrome c. Confirmed adrenal insufficiency
- 2. In participants with high-risk dysglycaemia at baseline, glycaemic responder status for each participant (defined as: a reduction in AUCglucose during the OGTT by ≥ 25% from baseline, without the addition of or an increase in the dose of glucose lowering medications) at week 30 and week 21 of treatment with osilodrostat or placebo.
- 3. Body weight responder status for each participant (defined a ≥ 5% decrease from baseline in body weight loss, without the addition of or an increase in the dose of weight lowering medications) at week 30 and week 21 with osilodrostat or placebo
- 4. The change from baseline in the SBP as measured by the average 24h- ABPM at week 30 and week 21, and the change over time in sitting SBP with osilodrostat or placebo
- 5. In participants with high risk dysglycaemia at baseline the change from baseline in glycaemia at week 30 and week 21 as measured by the glucose Area Under the Curve (AUCglucose) during an OGTT, glycated haemoglobin (HbA1c) and 2-hour post prandial glucose level (PPG). And over time by fasting plasma glucose (FPG) levels with osilodrostat or placebo
- 6. Change from baseline over time in body weight with osilodrostat or placebo
- 7. Frequencies and percentages of AEs, including AESI, laboratory, and ECG findings with osilodrostat or placebo. Changes from baseline in laboratory values, ECG readings, and in vital signs
- 8. Distribution of shifts in categories from baseline to week 30 and week 21 in the American Heart Association (AHA) and American Diabetes Association (ADA) classifications for hypertension and hyperglycaemia with osilodrostat or placebo
- 9. Distribution of dose changes (increase, decrease, or no change) and number of blood pressure and glucose lowering medications from baseline to week 30 and week 21 with osilodrostat or placebo
- 10. Normalization status of the 24h-UFC for each participant over time osilodrostat or placebo
- 11. BP responder status for each participant (defined as ≥ 5mmHg reduction in mean SBP and/or DBP as measured by ABPM - without worsening of either and without any modification in antihypertensive medications attributable to worsening hypertension) as measured at 21 weeks of treatment with osilodrostat or placebo
- Endpoints for exploratory objectives: 1. Composite cardiometabolic responder status for each participant (defined as BP responders, or glycaemia responders, or weight responders) at week 30 and week 21 of treatment with osilodrostat or placebo; a participant will be considered a responder if will be responder in at least one of the three responders typologies.
- 2. Responder status for each participant based on morning (8:00 AM) serum cortisol level ≤ 50 nmol/L (1.8 µg/dL) after a Low Dose Dexamethasone Suppression Test (LDDST) at 30 and 21 weeks of treatment with osilodrostat or placebo
- 3. The change from baseline at week 30 and 21 in the diurnal BP pattern as measured by the average daytime and average nighttime SBP and DBP during the 24h-ABPM with osilodrostat or placebo
- 4. Change from baseline in the 24h-urine adrenal steroid metabolome at 30 and 21 weeks of treatment with osilodrostat or placebo
- 5. The change from baseline at week 30 and week 21 in the DBP as measured by 24h-ABPM and in sitting DBP over time with osilodrostat or placebo
- 6. The change from baseline at week 30 and 21 of the morning, noon, afternoon, evening and late-night salivary cortisol and cortisone levels after treatment with osilodrostat or placebo
- 7. Changes in HRQoL (Cushing’s QoL and PHQ-9) from baseline to week 30 of treatment with osilodrostat or placebo. And the frequencies and percentages in HRQoL (PGIC) at week 30 of treatment with osilodrostat or placebo
- 8. Composite cardiometabolic responder status for each participant (defined as BP responders, and glycaemia responders, and weight responders) at week 30 and week 21 of treatment with osilodrostat or placebo; a participant will be considered a responder if will be responder in all the three responders typologies
研究者
Michal Sarnecki
Scientific
Recordati AG
研究点 (37)
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