Kerwin Edward M, Tashkin Donald P, Murphy Thomas R, Bensch George W, Marrs Tony, Luo Mary Z, Zhang Jack Y
Clinical Research Institute of Southern Oregon, Medford, Oregon.
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
J Aerosol Med Pulm Drug Deliv. 2020 Aug;33(4):186-193. doi: 10.1089/jamp.2019.1558. Epub 2020 Mar 6.
Two sequential single-dose crossover dose-ranging studies were performed to evaluate the clinical efficacy and safety profile of epinephrine hydrofluroalkane (HFA) metered-dose inhaler (MDI) formulation at various doses in subjects with asthma. In these multicenter, multiarm, double-blinded, or evaluator-blinded studies, subjects were randomized to receive the epinephrine HFA (Primatene MIST HFA) MDI medication at doses ranging from 90 to 440 μg/dose, as well as to a placebo (PLA) control and an active control of epinephrine CFC (chlorofluorocarbon) MDI (Primatene MIST CFC) at 220 μg/inhalation. Spirometry testing for FEV1 (Forced Expiratory Volume in one second) demonstrated statistically significant improvements over PLA for epinephrine HFA MDI at all doses above 125 μg, as the amount out of the actuator (i.e., mouthpiece). The efficacy results for epinephrine HFA MDI in the dose range of 125-250 μg were also comparable to epinephrine CFC MDI (220 μg/inh). Safety assessments demonstrated minimal safety concerns for all treatment groups. No notable safety differences were observed between the studied doses of epinephrine HFA MDI and the active control formulation of epinephrine CFC MDI. The findings indicate that epinephrine HFA MDI provided clinically significant bronchodilator efficacy with minimal safety concerns in a dose range of 125-250 μg. These findings confirmed the optimal treatment doses of 125-250 μg that were appropriate for use in longer term 12 and 26 week chronic dosing studies of epinephrine HFA MDI for patients with intermittent or mild to moderate persistent asthma. Clinical trials registration number: NCT01025648.
进行了两项连续的单剂量交叉剂量范围研究，以评估不同剂量的肾上腺素氢氟烷烃（HFA）定量吸入器（MDI）制剂对哮喘患者的临床疗效和安全性。在这些多中心、多臂、双盲或评估者盲法研究中，受试者被随机分配接受剂量范围为90至440μg/剂量的肾上腺素HFA（普米克令舒HFA）MDI药物，以及安慰剂（PLA）对照和220μg/吸入的肾上腺素氯氟烃（CFC）MDI（普米克令舒CFC）活性对照。对一秒用力呼气容积（FEV1）进行的肺量计测试表明，对于所有高于125μg的剂量，肾上腺素HFA MDI的FEV1相对于PLA有统计学上的显著改善，即从吸入器（即吸嘴）喷出的量。肾上腺素HFA MDI在125 - 250μg剂量范围内的疗效结果也与肾上腺素CFC MDI（220μg/吸入）相当。安全性评估表明所有治疗组的安全性问题极小。在研究的肾上腺素HFA MDI剂量与肾上腺素CFC MDI活性对照制剂之间未观察到明显的安全性差异。研究结果表明，肾上腺素HFA MDI在125 - 250μg剂量范围内提供了具有临床意义的支气管扩张疗效，且安全性问题极小。这些研究结果证实了125 - 250μg的最佳治疗剂量适用于肾上腺素HFA MDI对间歇性或轻度至中度持续性哮喘患者进行的为期12周和26周的长期慢性给药研究。临床试验注册号：NCT01025648。
