A Pharmacokinetic Study of Zavegepant Nasal Spray in Healthy Adults Comparing Conventional Venous Blood Sampling With Patient-Centric Microsampling

一项针对健康成年人的Zavegepant鼻喷雾剂药代动力学研究:比较传统静脉血采样与以患者为中心的微量采样

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Abstract

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(last)) and maximum serum/plasma concentration (C(max)) 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(last) and C(max) 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.

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