Novitt-Moreno Anne, Martidis Adam, Gonzalez Victor, Ransom Janet, Scott Charles B, Dow Geoffrey, Reid Mark, Smith Bryan, Zottig Victor E, Read Lisa Thomas, Garver Baldwin Lindsey S, Chen Fred K
Fast-Track Drugs & Biologics, Poolesville, MD, 20878, USA.
Retina Consultants of Southern Colorado, Colorado Springs, CO, 80909, USA.
Travel Med Infect Dis. 2022 Jan-Feb;45:102211. doi: 10.1016/j.tmaid.2021.102211. Epub 2021 Nov 18.
Tafenoquine is a long-acting 8-aminoquinoline approved for antimalarial prophylaxis for ≤6 months. Additional data is needed to establish the drug's longer-term safety profile, including potential ophthalmic or neuropsychiatric effects.
This was a randomized, double-blind, placebo-controlled trial in 600 healthy adults. Eligible subjects were randomized 1:1 to receive tafenoquine 200 mg weekly (antimalarial prophylactic regimen) or placebo for 52 weeks. Scheduled safety visits occurred at Weeks 4, 12, 24, 52 (dosing completed), and 64 (final follow-up). Safety assessments included ophthalmic changes, general and neuropsychiatric adverse events (AEs), and laboratory value changes.
The percentage of subjects with a protocol-defined Serious Ophthalmic Safety Event was lower in the Tafenoquine Group (18.2%) versus the Placebo Group (19%, p = 0.308). There was no significant difference between the percentages of subjects with at least one AE in the Tafenoquine Group (91.0%) versus Placebo (89.9%, p = 0.65). Common AEs seen at a significantly higher incidence for tafenoquine included reversible cornea verticillata (54.5%) and nausea (13.0%), leading to 0.0% and 0.7% discontinuations. Psychiatric AEs occurred at similar percentages in both study groups. Reversible changes in hemoglobin, methemoglobin, creatinine, and blood urea nitrogen (BUN) were noted.
This study supports the safety of extended 52-week tafenoquine prophylaxis. CLINICAL TRIAL REGISTRATION NUMBER/CLINICALTRIALS.
NCT03320174.
他非诺喹是一种长效8-氨基喹啉，已被批准用于≤6个月的疟疾预防。需要更多数据来确定该药物的长期安全性，包括潜在的眼科或神经精神方面的影响。
这是一项针对600名健康成年人的随机、双盲、安慰剂对照试验。符合条件的受试者按1:1随机分组，接受每周200毫克他非诺喹（抗疟疾预防方案）或安慰剂，持续52周。计划中的安全性访视在第4周、12周、24周、52周（给药完成）和64周（最终随访）进行。安全性评估包括眼科变化、一般和神经精神不良事件（AE）以及实验室值变化。
他非诺喹组中发生方案定义的严重眼科安全事件的受试者百分比（18.2%）低于安慰剂组（19%，p = 0.308）。他非诺喹组中至少发生一次AE的受试者百分比（91.0%）与安慰剂组（89.9%，p = 0.65）之间无显著差异。他非诺喹组中发生率显著更高的常见AE包括可逆性涡状角膜病变（54.5%）和恶心（13.0%），导致停药率分别为0.0%和0.7%。两个研究组中精神科AE的发生率相似。观察到血红蛋白、高铁血红蛋白、肌酐和血尿素氮（BUN）的可逆性变化。
本研究支持他非诺喹延长至52周预防的安全性。临床试验注册号/ClinicalTrials.gov标识符：NCT03320174。
