一项评估注射速度对健康志愿者大容量皮下给药Gantenerumab后疼痛、耐受性和药代动力学影响的I期研究
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波特雷on A, Jordan P, Draper K, Muenzer C, Dickerson D, van Iersel T, Hofmann C
一项评估注射速度对健康志愿者大容量皮下给药Gantenerumab后疼痛、耐受性和药代动力学影响的I期研究
中华临床杂志2020年1月;42(1):108-120.e1。doi: 10.1016 / j.clinthera.2019.11.015。Epub 2019 12月26日。
- PubMed ID
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31883703 (PubMed视图］
- 摘要
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目的:Gantenerumab是一种完全人抗β淀粉样蛋白IgG1单克隆抗体，与聚集形式的β淀粉样蛋白结合，正在研究作为早期(前驱症状到轻度)阿尔茨海默病(AD)的潜在疾病修饰治疗。我们的研究比较了5 s皮下注射和15 s皮下注射甘地单抗相关的疼痛，并评估了皮下注射甘地单抗的耐受性和药代动力学特性。方法:这项随机、开放标签、单次主动剂量、安慰剂对照交叉研究在50名40-80岁的健康志愿者中进行，无临床显著疾病史、药物或酒精滥用史、早发性AD家族史或先前接触甘特珠单抗。符合条件的参与者在5或15秒内被随机分配到一个300mg SC甘特珠单抗注射到腹部和2个SC安慰剂注射(1个注射到腹部，1个注射到大腿)。所有注射间隔至少90分钟。采用视觉模拟量表(VAS)和言语评分量表对参与者进行局部疼痛评估;通过记录不良事件(AEs)来评估安全性，并评估血浆药代动力学特性。结果:皮下注射甘特珠单抗后，注射5 s组和注射15 s组疼痛VAS评分在数值上更高，但没有达到统计学意义(VAS最小二乘平均差，7.492 mm;95% CI， -4.439-19.423 mm)。在两个注射速度组中，腹部皮下注射甘特珠单抗和安慰剂后的平均疼痛VAS评分相当。 Pain was reported after needle insertion and immediately after dosing, subsiding within 5 min after the dose. The pain VAS score was numerically higher after SC placebo injection into the thigh versus abdomen (5-s injection group: mean [SD] VAS score, 26.68 [27.83] vs 19.20 [25.60] mm; 15-s injection group: mean [SD] VAS score, 14.16 [20.62] vs 9.48 [12.04] mm). No serious AEs were reported; no participants withdrew because of an AE. All AEs were of mild intensity, were transient, and had resolved without sequelae at follow-up. The most common AEs were injection site reactions; redness was the most frequently observed skin reactivity event after subcutaneous gantenerumab administration (5-s injection group: 36%; 15-s injection group: 32%). After subcutaneous administration, gantenerumab reached a peak plasma concentration at a median time of 119 h (approximately 5 days); plasma concentrations declined in a monoexponential manner. Comparable pharmacokinetic profiles were observed between the injection speed groups. IMPLICATIONS: Subcutaneous gantenerumab injections at speeds of 5 and 15 s were well tolerated in healthy volunteers and could enable at-home administration by patients with AD or their caregivers. ClinicalTrials.gov identifier: NCT02882009.
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