Shahin Mohamed H, Fisniku Ogert, Ding Ding, Wan Katty, Dubrovin Sergey, Matschke Kyle, Kavetska Olga, Fountaine Robert, Liu Jing
Pfizer Inc., Groton, Connecticut, USA.
Pfizer Inc., Lake Forest, Illinois, USA.
Clin Transl Sci. 2025 Jun;18(6):e70199. doi: 10.1111/cts.70199.
This Phase 1, non-randomized, open-label, 2-period study compared the pharmacokinetics (PK) of zavegepant nasal spray, using samples collected via patient-centric microsampling (PCS) devices, with those collected through venous phlebotomy (NCT05948085). Fourteen healthy participants received a single intranasal dose of 10 mg zavegepant on Days 1 and 2. Blood samples for PK analysis were collected at 0.5, 1, 2, 4, 8, and 12 h post dose on Day 1 using the Tasso-Plus device (n = 7; produces serum samples), Tasso-M20 (n = 7; produces dried blood samples), and venous phlebotomy (n = 14). PK parameters were calculated using non-compartmental methods. Natural log-transformed areas under the plasma/serum concentration-time profile from time zero to the time of the last quantifiable concentration (AUC) and maximum serum/plasma concentration (C) of zavegepant were analyzed using a mixed-effects model, with blood collection as a fixed effect and participant as a random effect. Of the two PCS devices assessed, the results of the Tasso-Plus device showed successful bridging with venous phlebotomy sampling. For Tasso-Plus versus venous phlebotomy, 39 of 41 (95.1%) data pairs met concentration correlation criteria (difference within 20% of the mean), median zavegepant concentration-time profiles were comparable, and 90% confidence intervals for geometric mean ratios for AUC and C were wholly within the range of bioequivalence acceptance (80%-125%). The results of this study confirm that it is feasible to use serum derived from Tasso-Plus collection of whole capillary blood as a reliable PCS approach for PK analysis of zavegepant.
这项1期、非随机、开放标签、两阶段研究比较了扎韦潘特鼻喷雾剂的药代动力学（PK），使用通过以患者为中心的微量采样（PCS）设备采集的样本，与通过静脉采血采集的样本进行比较（NCT05948085）。14名健康参与者在第1天和第2天接受了单次10毫克扎韦潘特的鼻内给药。在第1天给药后0.5、1、2、4、8和12小时，使用Tasso-Plus设备（n = 7；产生血清样本）、Tasso-M20（n = 7；产生干血样本）和静脉采血（n = 14）采集用于PK分析的血样。使用非房室方法计算PK参数。使用混合效应模型分析扎韦潘特从时间零到最后可量化浓度（AUC）和最大血清/血浆浓度（C）的血浆/血清浓度-时间曲线下的自然对数转换面积，以采血作为固定效应，参与者作为随机效应。在所评估的两种PCS设备中，Tasso-Plus设备的结果显示与静脉采血采样成功衔接。对于Tasso-Plus与静脉采血，41对数据中的39对（95.1%）符合浓度相关标准（差异在平均值的20%以内），扎韦潘特浓度-时间曲线的中位数具有可比性，AUC和C的几何平均比值的90%置信区间完全在生物等效性接受范围内（80%-125%）。本研究结果证实，使用从Tasso-Plus采集的全毛细血管血中获得的血清作为扎韦潘特PK分析的可靠PCS方法是可行的。
