A Phase I, Randomized, Placebo-controlled, Open-label, Three Period Crossover Study to Investigate the Effect of Darolutamide and Enzalutamide on Cerebral Blood Flow in Healthy Male Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
研究概览
简要总结
The current study would investigate the effects of a single dose of darolutamide and enzalutamide compared with placebo and compared to each other on human brain blood flow using arterial spin labeling magnetic resonance imaging (ASL-MRI), a non-invasive MRI technique. The change in cerebral blood flow was an indirect measure of brain penetration.
The risk of drug-associated CNS-related adverse events was likely to be correlated with the concentration of the drug in the brain. In contrast to enzalutamide, preclinical studies of darolutamide indicate that its brain penetration was much lower.
The aim of this study was to determine whether there was a difference between darolutamide and enzalutamide compared to placebo in cerebral blood flow and thus in brain penetration.
详细描述
The primary objective was to investigate drug-induced changes in grey matter cerebral blood flow during single-dose treatment with darolutamide or enzalutamide as compared to placebo using voxel-wise quantification of the grey matter for the entire brain.
The secondary objective was to investigate drug-induced changes in regional cerebral blood flow in brain areas related to cognitive function after single-dose treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Participants who are healthy as determined by medical history, physical examination, laboratory tests, and cardiac monitoring.
排除标准
- •Existing or recent relevant diseases of vital organs (eg, liver diseases, heart diseases, renal disease, lung disease), central nervous system or other organs (eg, Diabetes mellitus, myasthenia gravis).
- •Known contraindication to magnetic resonance imaging.
- •Any structural variants or pathological abnormalities on structural brain MRI during screening.
- •Any history of seizures including a febrile seizure in childhood, loss of consciousness, transient ischemic attack, or any condition that may pre-dispose to seizure.
- •Participant with any type of neurological problems or history of psychiatric disorder, especially mood disorders including medical history with suicidal ideation and/or suicide attempts, which may disable the participant to consent to the study.
- •Participants who use prescription or oral over the counter medications which might influence the study objectives, dietary/nutritional supplements, (including vitamins, natural and herbal remedies, eg, St. John's wort) within 2 weeks prior to first study intervention administration or during the study.
研究组 & 干预措施
Men_EPD
Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_EPD
Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide.
干预措施: Enzalutamide (Drug)
Men_EPD
Healthy male participants receive drugs in order Enzalutamide, Placebo and Darolutamide.
干预措施: Placebo (Other)
Men_DEP
Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_DEP
Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo.
干预措施: Enzalutamide (Drug)
Men_DEP
Healthy male participants receive drugs in order Darolutamide, Enzalutamide and Placebo.
干预措施: Placebo (Other)
Men_PDE
Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_PDE
Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide.
干预措施: Enzalutamide (Drug)
Men_PDE
Healthy male participants receive drugs in order Placebo, Darolutamide and Enzalutamide.
干预措施: Placebo (Other)
Men_DPE
Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_DPE
Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide.
干预措施: Enzalutamide (Drug)
Men_DPE
Healthy male participants receive drugs in order Darolutamide, Placebo and Enzalutamide.
干预措施: Placebo (Other)
Men_EDP
Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_EDP
Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo.
干预措施: Enzalutamide (Drug)
Men_EDP
Healthy male participants receive drugs in order Enzalutamide, Darolutamide and Placebo.
干预措施: Placebo (Other)
Men_PED
Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.
干预措施: Darolutamide (BAY1841788) (Drug)
Men_PED
Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.
干预措施: Enzalutamide (Drug)
Men_PED
Healthy male participants receive drugs in order Placebo, Enzalutamide and Darolutamide.
干预措施: Placebo (Other)
结局指标
主要结局
Change in grey-matter cerebral blood flow of enzalutamide as compared to placebo
时间窗: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to placebo. Measured in grey matter voxels with arterial spin labeling magnetic resonance imaging (ASL-MRI).
Change in grey-matter cerebral blood flow of darolutamide as compared to placebo
时间窗: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of darolutamide to placebo. Measured in grey matter voxels with ASL-MRI.
Change in grey-matter cerebral blood flow of enzalutamide as compared to darolutamide
时间窗: At 4 hours after drug
Obtained by comparing whole brain grey matter quantitative voxel-by-voxel maps of cerebral blood flow/ perfusion (mL per 100g tissue per min) of enzalutamide to darolutamide. Measured in grey matter voxels with ASL-MRI.
次要结局
- Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of darolutamide as compared to placebo(At 4 hours after drug)
- Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to darolutamide(At 4 hours after drug)
- Change in mean regional grey-matter cerebral blood flow in brain areas related to cognitive function during treatment of enzalutamide as compared to placebo(At 4 hours after drug)