Schoedel Kerri A, Rolleri Robert L, Faulknor Janice Y, Pixton Glenn C, Chen Nancy, Bass Almasa, Sommerville Kenneth W, Sellers Edward
INC Research, Toronto, Ontario, Canada.
J Opioid Manag. 2012 Sep-Oct;8(5):315-27. doi: 10.5055/jom.2012.0131.
To evaluate the pharmacodynamic effects (subjective and physiologic) of a new formulation of immediate release oxycodone HCl (IRO-A; Oxecta™) tablets compared with immediate release oxycodone HCl (IRO; Roxicodone®) tablets when crushed and administered intranasally to nondependent recreational opioid users.
Single-center, single-dose, randomized, double-blind, active-controlled two-way crossover study.
Inpatient Clinical Pharmacology Unit, Toronto, Canada.
Nondependent, recreational opioid users aged 18-55 years.
Subjects able to discriminate intranasally administered crushed IRO from placebo were randomized to receive 15 mg crushed IRO-A and crushed IRO in crossover fashion in treatment phase.
Primary subjective endpoints were maximum effect (E(max)) for Drug Liking and effect at 8 hours (E(8h)) postdose for Take Drug Again and Overall Drug Liking. All were assessed using bipolar 0-100 visual analog scale (VAS; 50 points = neutral). Secondary pharmacodynamic endpoints included other VAS endpoints, pupillometry, and subject-rated scales for nasal effects.
Forty subjects were randomized to treatment; 39 were evaluable, one subject was excluded for postdose vomiting. Subjects were mostly male (80 percent) and White (75 percent). Least squares mean Drug Liking VAS E(max) (70.8 vs 93.5), Overall Drug Liking E(8h) (47.8 vs 87.4), and Take Drug Again E(8h) (45.9 vs 91.3) were significantly lower for crushed IRO-A vs IRO (all p < 0.0001). A significant sequence effect was found, but lower liking of IRO-A was observed for both treatment sequence groups. Pupillary responses between treatments were similar overall, but differences were noted for some endpoints/time points. Adverse events common to opioids were observed with both treatments. Subjects experienced more nasal-related symptoms with IRO-A.
Crushed IRO-A tablets demonstrated lower scores on "drug liking," "overall drug liking," and "take drug again" than crushed IRO when administered intranasally to nondependent recreational opioid users.
评估将速释盐酸羟考酮（IRO - A；Oxecta™）片的新剂型与速释盐酸羟考酮（IRO；Roxicodone®）片碾碎后经鼻给予非依赖性娱乐性阿片类药物使用者时的药效学效应（主观和生理方面）。
单中心、单剂量、随机、双盲、活性对照双向交叉研究。
加拿大多伦多的住院临床药理学单元。
年龄在18至55岁之间的非依赖性娱乐性阿片类药物使用者。
能够区分经鼻给予的碾碎IRO与安慰剂的受试者在治疗阶段以交叉方式随机接受15毫克碾碎的IRO - A和碾碎的IRO。
主要主观终点为药物喜好的最大效应（E(max)）以及再次服药和总体药物喜好在给药后8小时（E(8h)）的效应。所有指标均使用双极0 - 100视觉模拟量表（VAS；50分为中性）进行评估。次要药效学终点包括其他VAS终点、瞳孔测量以及受试者对鼻部效应的评分量表。
40名受试者被随机分配至治疗组；39名可评估，1名受试者因给药后呕吐被排除。受试者大多为男性（80%）且为白人（75%）。碾碎的IRO - A与IRO相比，最小二乘均值药物喜好VAS E(max)（70.8对93.5）、总体药物喜好E(8h)（47.8对87.4）以及再次服药E(8h)（45.9对91.3）均显著更低（所有p < 0.0001）。发现了显著的序列效应，但两个治疗序列组对IRO - A的喜好均较低。总体而言，两种治疗之间的瞳孔反应相似，但在某些终点/时间点存在差异。两种治疗均观察到阿片类药物常见的不良事件。IRO - A组受试者出现更多与鼻部相关的症状。
将碾碎的IRO - A片经鼻给予非依赖性娱乐性阿片类药物使用者时，其在“药物喜好”、“总体药物喜好”和“再次服药”方面的得分低于碾碎的IRO。
