Teva Pharmaceuticals, Inc., Malvern, Pennsylvania, USA.
Altreos Research Partners, Inc., Toronto, ON, Canada.
Pain Med. 2018 Aug 1;19(8):1597-1612. doi: 10.1093/pm/pnx133.
To assess the intranasal abuse potential of hydrocodone extended-release (ER) tablets developed with CIMA Abuse-Deterrence Technology compared with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER, original formulation [HYD-OF]).
Single-dose, randomized, double-blind, quadruple-dummy, active- and placebo-controlled, crossover study.
One US site.
Healthy, adult, nondependent, recreational opioid users.
Subjects able to tolerate intranasal hydrocodone and discriminate hydrocodone from placebo were eligible for study enrollment. Eligible participants randomly received intranasal hydrocodone ER, intranasal hydrocodone powder, intranasal HYD-OF, intact oral hydrocodone ER, and placebo. Coprimary pharmacodynamic end points were a maximum effect on "at the moment" Drug Liking visual analog scale and Overall Drug Liking visual analog scale. Pharmacokinetics and safety were assessed.
Mean maximum effect for "at the moment" Drug Liking was significantly (P < 0.01) lower for intranasal hydrocodone ER (72.8) compared with hydrocodone powder (80.2) and HYD-OF (83.2). Similar results were observed for Overall Drug Liking maximum effect (68.5 vs 77.1 and 79.8, respectively; P < 0.01). Secondary end points, including balance of effects and positive, sedative, and other effects, were consistent with these results. Intranasal treatments showed significantly greater effects vs placebo, while intact oral hydrocodone ER was similar to placebo. For each treatment, plasma concentration-time profiles paralleled "at the moment" Drug Liking over time. Incidences of adverse events for intranasal treatments were 52% for hydrocodone ER, 53% for hydrocodone powder, and 61% for HYD-OF.
The statistically significant differences between hydrocodone ER vs hydrocodone powder and HYD-OF for the primary drug liking end points indicate a lower intranasal abuse potential with hydrocodone ER in healthy, nondependent, recreational opioid users.
评估采用 CIMA 防滥用技术开发的氢可酮缓释片（ER）相较于氢可酮粉末和氢可酮酒石酸盐 ER 胶囊（Zohydro ER，原始配方[HYD-OF]）的经鼻滥用潜力。
单次给药、随机、双盲、四重双模拟、阳性和安慰剂对照、交叉研究。
美国的一个研究场所。
健康、成年、非依赖、消遣性阿片类药物使用者。
能够耐受经鼻氢可酮且能够区分氢可酮与安慰剂的受试者有资格参加研究。合格的参与者随机接受经鼻氢可酮 ER、经鼻氢可酮粉末、经鼻 HYD-OF、完整口服氢可酮 ER 和安慰剂。主要药效学终点是“此刻”药物喜好视觉模拟评分和总体药物喜好视觉模拟评分的最大效应。评估了药代动力学和安全性。
“此刻”药物喜好的平均最大效应，经鼻氢可酮 ER（72.8）明显低于氢可酮粉末（80.2）和 HYD-OF（83.2）（P<0.01）。总体药物喜好的最大效应也观察到了类似的结果（分别为 68.5、77.1 和 79.8；P<0.01）。次要终点，包括效应平衡和阳性、镇静和其他效应，与这些结果一致。经鼻治疗与安慰剂相比显示出显著更大的效应，而完整口服氢可酮 ER 与安慰剂相似。对于每种治疗，血浆浓度-时间曲线随时间与“此刻”药物喜好平行。经鼻治疗的不良事件发生率为氢可酮 ER 组 52%、氢可酮粉末组 53%和 HYD-OF 组 61%。
对于主要药物喜好终点，氢可酮 ER 与氢可酮粉末和 HYD-OF 之间的统计学显著差异表明，在健康、非依赖、消遣性阿片类药物使用者中，氢可酮 ER 的经鼻滥用潜力较低。
