A Phase 1b/2a Open-label Multiple-ascending Dose Exploratory Study of CRN04894 in ACTH-dependent Cushing's Syndrome (Cushing's Disease or Ectopic ACTH Syndrome)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Proportion of participants with adrenal insufficiency
研究概览
简要总结
A Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with CRN04894 (an adrenocorticotropic hormone [ACTH] receptor antagonist) in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS])
详细描述
This is a Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with atumelnant (also known as CRN04894) (an adrenocorticotropic hormone [ACTH] receptor antagonist) over a 10-day or 14-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS]). Participants will receive oral atumelnant once daily for 10 days followed by monitoring during 4 'wash-out' days, or for 14 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female, aged 18 years or more
- •Evidence of chronic 'active' ACTH-dependent Cushing's syndrome
- •Evidence of acutely 'active' ACTH-dependent Cushing's syndrome within 10 days of Day 1
- •Participants with documented ACTH-dependent Cushing's syndrome taking short-acting steroidogenesis inhibitors (ketoconazole, levoketoconazole, osilodrostat, or metyrapone) may participate after a washout period of at least 5 days, if they meet other study inclusion criteria, relative to Investigator's judgment. Participants with documented ACTH-dependent Cushing's syndrome taking cabergoline may participate after a washout period of at least 14 days, if they meet other study inclusion criteria
排除标准
- •Women who are pregnant or lactating
- •History of bilateral adrenalectomy
- •Previous pituitary MRI findings of a putative ACTH-secreting lesion within 3 mm of the optic chiasm
- •Presence of any known malignancy
- •Use of mitotane
- •Previous unsuccessful surgery for Cushing's syndrome within 6 weeks
研究组 & 干预措施
Multiple Ascending Doses
Sequential, open-label, 10-day or 14-day fixed-dose cohorts.
干预措施: atumelnant (Drug)
结局指标
主要结局
Proportion of participants with adrenal insufficiency
时间窗: Up to Day 15
Proportion of participants with treatment emergent adverse events (TEAEs)
时间窗: Up to Day 15
Proportion of participants with safety findings determined by laboratory testing
时间窗: Up to Day 15
Assessment of the time to achieve maximum observed plasma concentration of CRN04894
时间窗: Up to Day 15
Assessment of the maximum observed plasma concentration of CRN04894
时间窗: Up to Day 15
Assessment of the plasma area under the curve of CRN04894
时间窗: Up to Day 15
次要结局
- Change from baseline in early morning serum cortisol(Up to Day 15)