引用

本研究评估了布洛芬一种新型固定剂量组合(FDC)的解热疗效和起效(IBU;250毫克)和对乙酰氨基酚(APAP;500 mg)与安慰剂和IBU或APAP单组分比较。MET:这项单中心、随机、双盲、安慰剂对照、全因子研究是在18 - 55岁的健康男性中进行的，他们因静脉注射参考标准内毒素(RSE)引起发热。在口腔温度达到38.1℃后，受试者被随机分为3:3:3:1单次口服FDC IBU/APAP 250mg / 500mg、APAP 500mg、IBU 250mg或安慰剂双盲组。口服温度每10分钟测量一次，持续2小时，然后每30分钟测量一次，直到给药后8小时。研究给药后从基线到8小时(WSTD0-8)的时间加权温度差之和是主要疗效终点。次要终点包括0 ~ 2小时、0 ~ 4小时、0 ~ 6小时和6 ~ 8小时的WSTD评分;恢复“正常”温度的时间;抢救用药时间; and global drug evaluation. Safety was assessed via adverse events (AEs).Two hundred ninety subjects were randomized; 273 were included in the primary efficacy analysis. WSTD0-8 was significantly better for FDC IBU/APAP 250 mg/500 mg (P?=?0.002), IBU 250 mg (P?=?0.030), and APAP 500 mg (P?=?0.023) versus placebo; there were no significant differences between active treatments. For WSTD0-2, only the FDC was statistically significant versus placebo (P?=?0.004). All active treatments were significantly better (P < 0.05) for WSTD0-4 and WSTD0-6 versus placebo; there were no differences in WSTD6-8 between cohorts. Temperature returned to normal during the 8-hour treatment period in ?50% of subjects in each cohort. Only 1 subject (IBU cohort) took rescue medication. Post hoc analyses at early time points revealed significant treatment differences favoring FDC versus placebo and IBU for the WSTD from baseline during the 50- to 110-minute posttreatment window; for WSTD from baseline during the 80- to 110-minute posttreatment window, FDC provided significant treatment differences versus placebo and both monocomponents. Overall, 223 (76.9%) of 290 subjects experienced AEs related to RSE; only 2 subjects experienced treatment-related AEs (FDC, rash; placebo, ear pain).Although the primary end point was not met, these results suggest that FDC IBU/APAP 250 mg/500 mg provides effective antipyresis with a faster onset versus equal doses of IBU and APAP alone. ClinicalTrials.gov identifier: NCT02761980. (Clin Ther. 2021;43:XXX-XXX)