Ocwieja Magdalena, Meiser Karin, David Olivier J, Valencia Jessica, Wagner Frank, Schreiber Stephan J, Pleyer Uwe, Ziemer Sabine, Schmouder Robert
Novartis Pharma AG, Basel, Switzerland.
Br J Clin Pharmacol. 2014 Dec;78(6):1354-65. doi: 10.1111/bcp.12454.
Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers.
The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value).
All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports.
In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.
芬戈莫德是一种鞘氨醇-1-磷酸受体调节剂，是首个被批准用于治疗复发型多发性硬化症的口服疾病修正疗法。本双盲、安慰剂对照研究的目的是评估芬戈莫德对健康志愿者脑血流量、血小板功能和黄斑厚度的影响。
该研究纳入了88名健康志愿者，他们在4周内接受了0.5毫克或1.25毫克的芬戈莫德或匹配的安慰剂。采用经颅彩色编码超声测量平均血流速度，使用胶原蛋白/肾上腺素检测卡通过PFA-100®检测法测量血小板功能，并使用光学相干断层扫描测量黄斑厚度。针对参考值（总体基线值的20%）对芬戈莫德与安慰剂进行非劣效性评估。
所有88名随机参与者均完成了研究。在第28天，与基线值相比，0.5毫克、1.25毫克和安慰剂治疗组的大脑中动脉平均血流速度分别下降了4、1和3.7厘米/秒。血小板功能分析仪的关闭时间增加不显著（分别为7.8、7.5和10.4秒）。所有组双眼中央凹厚度相对于基线的平均百分比变化均低于3%。本研究中芬戈莫德的安全性与先前报告一致。
在健康志愿者中，两种芬戈莫德剂量所观察到的变化在正常变异性范围内，对于所有评估的药效学参数，与安慰剂相比为非劣效且相当。
