Singla Neil, Margulis Rachel, Kostenbader Kenneth, Zheng Yanping, Barrett Thomas, Giuliani Michael J, Chen Yin, Young Jim L
Department of Anesthesia, Lotus Clinical Research LLC, Huntington Hospital , Pasadena, CA , USA.
Phys Sportsmed. 2015 May;43(2):126-37. doi: 10.1080/00913847.2015.1025029. Epub 2015 Mar 22.
A fixed-dose combination biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) tablet is being developed for the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate.
This Phase III, randomized, double-blind, placebo-controlled, parallel-group study evaluated the analgesic efficacy and safety of IR/ER HB/APAP (n = 201) versus placebo (n = 202) over a period of 48 hours in patients with acute moderate to severe pain following unilateral bunionectomy. Patients received three tablets of placebo or IR/ER HB/APAP as an initial dose (hour 0) followed by two tablets every 12 hours for a total daily dose of 37.5/1625 mg HB/APAP on day 1 and 30/1300 mg HB/APAP thereafter. The primary efficacy outcome was the summed pain intensity difference (SPID) over the first 48 hours (SPID48) after the first dose.
SPID48 was significantly greater with IR/ER HB/APAP versus placebo (p < 0.001). SPID dosing interval analyses demonstrated consistent, superior pain relief with IR/ER HB/APAP for each dosing interval (all p < 0.001). Mean PID was greater with IR/ER HB/APAP versus placebo beginning 30 minutes after the first dose (p < 0.05), and IR/ER HB/APAP demonstrated faster median time to the onset of perceptible, meaningful, and confirmed pain relief (all p < 0.001). Mean total pain relief scores also indicated greater pain relief with IR/ER HB/APAP versus placebo throughout the 48-hour period (p = 0.012) for all comparisons. A greater proportion of IR/ER HB/APAP versus placebo patients was either "very satisfied" or "satisfied" with their pain relief (69.3% vs 49.4%; p < 0.001). Nausea was the most common treatment-emergent adverse event (TEAE; IR/ER HB/APAP, 25%; placebo, 7.9%). All TEAEs in IR/ER HB/APAP-treated patients were mild or moderate in severity.
IR/ER HB/APAP provided rapid, significant, and consistent analgesic efficacy over a period of 48 hours in an established model of acute pain and was tolerated with a safety profile similar to other low-dose opioids.
一种固定剂量复方双相速释（IR）/缓释（ER）氢可酮 bitartrate（HB）/对乙酰氨基酚（APAP）片剂正在研发中，用于治疗严重到需要阿片类药物治疗且其他治疗选择不足的急性疼痛。
这项 III 期、随机、双盲、安慰剂对照、平行组研究评估了 IR/ER HB/APAP（n = 201）与安慰剂（n = 202）在单侧拇囊炎切除术后急性中度至重度疼痛患者中 48 小时内的镇痛疗效和安全性。患者在初始剂量（第 0 小时）接受三片安慰剂或 IR/ER HB/APAP，随后每 12 小时两片，第 1 天的总日剂量为 37.5/1625 mg HB/APAP，此后为 30/1300 mg HB/APAP。主要疗效指标是首剂后前 48 小时（SPID48）的疼痛强度差值总和。
与安慰剂相比，IR/ER HB/APAP 的 SPID48 显著更高（p < 0.001）。SPID 给药间隔分析表明，IR/ER HB/APAP 在每个给药间隔均能持续提供更优的疼痛缓解（所有 p < 0.001）。首剂后 30 分钟起，IR/ER HB/APAP 的平均疼痛强度差值（PID）高于安慰剂（p < 0.05），且 IR/ER HB/APAP 显示出可感知、有意义且确定的疼痛缓解起效中位时间更快（所有 p < 0.001）。在整个 48 小时期间，所有比较中 IR/ER HB/APAP 的平均总疼痛缓解评分也表明其疼痛缓解程度高于安慰剂（p = 0.012）。与安慰剂组相比，更多接受 IR/ER HB/APAP 治疗的患者对疼痛缓解“非常满意”或“满意”（69.3% 对 49.4%；p < 0.001）。恶心是最常见的治疗中出现的不良事件（TEAE；IR/ER HB/APAP 组为 25%，安慰剂组为 7.9%）。接受 IR/ER HB/APAP 治疗的患者中所有 TEAE 的严重程度均为轻度或中度。
在既定的急性疼痛模型中，IR/ER HB/APAP 在 48 小时内提供了快速、显著且持续的镇痛疗效，其耐受性与其他低剂量阿片类药物相似。
