临床药理学和耐受性REC-994,一个氧化还原循环氧化物化合物,在随机第一阶段剂量发现研究中
Ron Alfa1, Timothy Considine1, Shafique Virani1
1Recursion Pharmaceuticals, Inc., Salt Lake City, Utah, USA.
Pharmacology research & perspectives
|April 24, 2024
概括
REC-994 (tempol) 是一种潜在的治疗大脑洞腔形 (CCM) 的方法. 这项研究发现,REC-994在健康志愿者中安全且耐受良好,这支持了对有症状的CCM患者的进一步临床试验.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 神经学 神经学
- 血管生物学 血管生物学
背景情况:
- 大脑洞腔形 (CCM) 带来了重大的临床挑战,包括危及生命的出血性中风,治疗选择有限.
- 超氧化物,一种反应性氧物种,与CCM病原发生有关,这突显了针对性干预的必要性.
- REC-994 (tempol) 已成为CCM的潜在治疗剂,假设通过降低超氧化物水平来发挥其作用.
研究的目的:
- 在健康的成年志愿者中评估REC-994的安全性和耐受性.
- 在单次和多次上升剂量后,描述REC-994的药理学特征.
- 提供支持REC-994在症状CCM患者的潜在疗效的数据.
主要方法:
- 进行了两项1期临床研究:单次上升剂量 (SAD) 研究和多次上升剂量 (MAD) 研究.
- 健康的志愿者 (18-55岁) 接受了REC-994或安慰剂的口服剂量.
- 该MAD研究涉及10天的每日剂量,并进行了药理动力学和安全性评估.
主要成果:
- 在SAD和MAD研究中,REC-994在50-800毫克的剂量范围内证明了剂量相对应的全身暴露.
- 药物耐受性良好,所有治疗出现的不良反应都是轻微的和短暂的.
- 没有发现剂量限制的不良反应,像Tmax和t1/2这样的药理学参数是剂量独立的.
结论:
- REC-994具有良好的安全性,在健康志愿者中耐受性很好,高达800毫克.
- 药物动力学数据支持REC-994.4的进一步开发.
- 这些发现为在患有症状性脑洞形形的患者中启动第二期临床试验提供了强有力的理由.
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