Patel Piyush, Salapatek Anne Marie, Talluri Ravi S, Tantry Sudeesh K
From the Inflamax Research Inc., Mississauga, Ontario, Canada.
Glenmark Pharmaceuticals Ltd., Navi Mumbai, India.
Allergy Asthma Proc. 2018 May 1;39(3):232-239. doi: 10.2500/aap.2018.39.4134.
GSP301 is a fixed-dose combination (FDC) of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray (NS).
To assess the relative bioavailability of mometasone administered as GSP301 FDC versus two mometasone monotherapy NS formulations.
In this single-dose, open-label, crossover study, healthy adults (age range, 18-65 years) were randomized equally to one of six treatment sequences for three 72-hour treatment periods with GSP301 (olopatadine 665 μg-mometasone 50 μg), the mometasone furoate monotherapy component of GSP301 (MF-sponsor, 50 μg), and U.S. Food and Drug Administration-approved mometasone (MF, 50 μg); all the treatments were administered as two sprays per nostril. To evaluate the relative bioavailability of mometasone, pharmacokinetic (PK) estimates, the maximum plasma concentration (Cmax), the area under the plasma concentration time curve (AUC) from time 0 to the last time point with measurable concentration (AUC0-t), and AUC from time 0 to time infinity (AUC0-∞) were compared by analysis of variance. Safety and tolerability were also assessed.
A total of 30 healthy subjects were randomized. Most subjects were white men who were not obese, mean age of ∼43 years. The geometric mean ratios for natural log transformed Cmax, AUC0-t, and AUC0-∞ of mometasone in GSP301 to MF-sponsor were 113.83, 118.36, and 118.50, respectively. For GSP301 and MF, geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 141.84, 109.92, and 115.14, respectively. The percentages of subjects who reported treatment-emergent adverse events (TEAE) were 10.0%, 13.3%, and 10.3% for GSP301, MF-sponsor, and MF treatments, respectively. All TEAEs were mild, and none resulted in discontinuation.
Mometasone bioavailability with GSP301 was comparable with MF-sponsor and MF monotherapies. A slightly higher Cmax was observed with GSP301 than with MF, but AUC was comparable. The addition of olopatadine to mometasone in GSP301 did not considerably affect the PK of mometasone. GSP301 was well tolerated, with only mild adverse events reported.
GSP301是一种抗组胺药盐酸奥洛他定和皮质类固醇糠酸莫米松的固定剂量复方制剂（FDC），开发为单一鼻喷雾剂（NS）。
评估GSP301 FDC中糠酸莫米松与两种糠酸莫米松单药疗法鼻喷雾剂制剂相比的相对生物利用度。
在这项单剂量、开放标签、交叉研究中，健康成年人（年龄范围18 - 65岁）被平均随机分配到六个治疗序列之一，接受三个72小时的治疗期，分别使用GSP301（奥洛他定665μg - 糠酸莫米松50μg）、GSP301中的糠酸莫米松单药疗法成分（MF - 申办方，50μg）以及美国食品药品监督管理局批准的糠酸莫米松（MF，50μg）；所有治疗均为每侧鼻孔喷两下。为评估糠酸莫米松的相对生物利用度，通过方差分析比较药代动力学（PK）估计值、最大血浆浓度（Cmax）、从时间0到最后一个可测浓度时间点的血浆浓度时间曲线下面积（AUC0 - t）以及从时间0到无穷大的AUC（AUC0 - ∞）。还评估了安全性和耐受性。
共有30名健康受试者被随机分组。大多数受试者为非肥胖白人男性，平均年龄约43岁。GSP301中糠酸莫米松的自然对数转换后的Cmax、AUC0 - t和AUC0 - ∞与MF - 申办方的几何平均比值分别为113.83、118.36和118.50。对于GSP301和MF，Cmax、AUC0 - t和AUC0 - ∞的几何平均比值分别为141.84、109.92和115.14。报告治疗中出现不良事件（TEAE）的受试者百分比在GSP301、MF - 申办方和MF治疗组中分别为10.0%、13.3%和10.3%。所有TEAE均为轻度，无一导致停药。
GSP301中糠酸莫米松的生物利用度与MF - 申办方和MF单药疗法相当。观察到GSP301的Cmax略高于MF，但AUC相当。在GSP301中糠酸莫米松添加奥洛他定并未显著影响糠酸莫米松的药代动力学。GSP301耐受性良好，仅报告了轻度不良事件。
