多次皮下注射重组人甲状旁腺素(1-34)在健康人体的耐受性

Tolerability of recombinant human parathyroid hormone(1-34)following multiple subcutaneous administrations in healthy Chinese subjects

目的:评价中国健康志愿者多次皮下注射重组人甲状旁腺素(1-34)的安全性及耐受性。方法:单中心、开放的试验设计,选择6名符合入选标准的健康志愿者,男女各半。餐后给予重组人甲状旁腺素(1-34)40μg,每日1次,连续给药7日。观察给药前后受试者生命体征、实验室及心电图检查的变化,记录受试者在给药后的自我感觉及不良事件。结果:6例受试者均完成本次试验,给药前后生命体征、心电图及实验室检查均无有临床意义的变化。试验期间仅有轻度的不良反应发生,表现为3例受试者出现注射部位轻度红斑,其中1例受试者出现轻度恶心呕吐,1例受试者出现食欲不振等。试验中未见严重不良反应。结论:重组人甲状旁腺素(1-34)多次皮下注射(40μg,qd,连续给药7 d)在中国健康志愿者的安全性和耐受性良好,为Ⅱ期临床试验剂量选择提供实验依据。

OBJECTIVE To investigate the safety and tolerability of multiple subcutaneous doses of recombinant human par- athyroid hormone （l-34） [rhPTH（1-34）] 40 /tg in healthy Chinese volunteers. METHODS The study was a single-centre, open-label experimental design. Six healthy volunteers （3 men and 3 women） were enrolled and accepted multiple doses of rhPTH（1-34） 40/tg once daily after breakfast for 7 consecutive days. The changes of vital signs and 12-lead electrocardiogram （ECG） findings as well as laboratory findings were monitored at the time of pre-and post-dose. At the same time, the adverse events were observed and recorded. RESULTS All six subjects completed the study as planned. Assessments of vital signs, ECG findings, laboratory findings after drug administration did not show any clinically relevant differences from the baseline values. A total of 3 subjects experienced mild adverse events manifested by erythema in injection site, among them 1 subject ap- peared mild nausea and vomiting, 1 subject suffered loss of appetite. No severe adverse events occurred in the study. CONCLUSION Subcutaneous administration of rhPTH（1-34） was safe and well tolerated in healthy Chinese volunteers with the dose of 40/tg once daily for 7 consecutive days. According to this study a recommended dose of 20,40/~g for phase II clini- cal trials was obtained.