Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza
Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza
复制标题
DOI：
10.1001/jama.275.4.295
复制
发表时间：
1996-01-24
影响因子：
120.7
通讯作者：
Hussey, EK
中科院分区：
文献类型：
--
作者：
Hayden, FG;Treanor, JJ;Hussey, EK
目标。目前的研究评估了唾液酸类似物4-胍- neu5ac2en (GG167)，一种流感病毒神经氨酸酶抑制剂，在预防或治疗实验性人流感方面是否有效和安全。-进行了四项随机、双盲、安慰剂对照试验，包括三个预防肢、两个早期治疗肢和一个延迟治疗肢。-单独房间隔离参与者-对易感（血清血凝抑制抗体滴度小于或等于1:8）的成年志愿者（n=166）进行鼻内接种10(5)TCID50甲型流感/得克萨斯/91 （H1N1）病毒。GG167, 3.6 ~ 16mg，在接种前4小时（预防）或接种后1 ~ 2天（早期或延迟治疗）开始每日鼻内给药2 ~ 6次。主要的结果。-病毒学措施是基于病毒脱落和/或血清转化的感染频率（预防）或基于滴度和病毒恢复持续时间的定量病毒脱落（治疗）。临床指标为发热性疾病出现频率及症状严重程度评分。-鼻内GG167对预防和治疗均具有良好的耐受性，对于所有剂量组，GG167预防在预防实验室感染证据方面的有效性为82%，在预防发热性疾病方面的有效性为95%
Objective. - The current study evaluated whether intranasal administration of the sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus neuraminidase, was effective and safe in either preventing or treating experimental human influenza.Methods. - Four randomized, double-blind, placebo-controlled trials involving three prophylaxis limbs, two early treatment limbs, and one delayed treatment limb were conducted.Setting. - Isolation in individual rooms.Participants. - Susceptible (serum hemagglutination-inhibition antibody titer less than or equal to 1:8) adult volunteers (n=166) were inoculated intranasally with 10(5) TCID50 influenza A/Texas/91 (H1N1) virus.Intervention. - GG167, 3.6 to 16 mg, was administered intranasally two or six times daily beginning 4 hours before inoculation (prophylaxis) or 1 or 2 days afterward (early or delayed treatment).Main Outcomes. - Virological measures were frequency of infection based on viral shedding and/or seroconversion (prophylaxis) or quantitative viral shedding based on titers and duration of virus recovery (treatment). Clinical measures were the frequency of febrile illness and symptom severity scores.Results. - Intranasal GG167 was well tolerated for both prophylaxis and therapy, For all dose groups combined, GG167 prophylaxis was 82% effective in preventing laboratory evidence of infection and 95% effective in preventing febrile illness (P