International Clinical Research Institute, Overland Park, KS, USA ; Kansas University Medical Center, Kansas City, KS, USA.
Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
J Pain Res. 2014 Nov 21;7:669-78. doi: 10.2147/JPR.S71536. eCollection 2014.
To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid.
This multicenter, open-label study started with a conversion/titration phase (≤6 weeks) where subjects (n=638) were converted to individualized doses (range 20-300 mg) of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424). The primary objective (safety and tolerability) and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain) were monitored throughout the study.
Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%), nausea (10.7% and 9.9%), vomiting (4.1% and 9.7%), and somnolence (7.7% and 4.2%). Four deaths occurred during the study; all were considered unrelated to treatment. One subject died 13 months after the study ended. From the start to end of the conversion/titration phase, 84% of subjects had a clinically meaningful improvement in average pain score (≥30% improvement), and the mean average pain scores remained stable through the maintenance phase.
This single-entity, extended-release formulation of hydrocodone was generally safe, well tolerated, and effective in reducing chronic pain for 48 weeks. This formulation provides a new option for patients experiencing chronic pain, especially those who are taking immediate-release hydrocodone and have concerns about liver toxicity due to acetaminophen.
评估单一实体缓释氢可酮在慢性疼痛中度至重度且阿片类药物治疗经验丰富但未获得充分疼痛缓解或当前阿片类药物治疗不耐受的患者中的长期安全性、耐受性和有效性。
这项多中心、开放性研究首先进行了转换/滴定阶段（≤6 周），在此期间，受试者（n=638）转换为个体化剂量（范围 20-300mg）的氢可酮缓释制剂，每 12 小时给药一次，随后进行 48 周的维持阶段（n=424）。主要目标（安全性和耐受性）和次要目标（通过平均疼痛评分变化衡量的长期疗效；0=无疼痛，10=可想象的最严重疼痛）在整个研究期间进行监测。
受试者接受了各种慢性疼痛病因的治疗，包括骨关节炎、腰痛以及神经病理性和肌肉骨骼疾病。筛选时的氢可酮等效剂量为 68.9±62.2mg/天，在维持阶段开始时增加至 139.5±81.7mg/天。在维持阶段，根据研究者的判断可以不受限制地调整剂量，这反映了典型的临床实践。未报告意外的安全性问题。在转换/滴定和维持阶段分别常见的不良反应是便秘（11.3%和 12.5%）、恶心（10.7%和 9.9%）、呕吐（4.1%和 9.7%）和嗜睡（7.7%和 4.2%）。研究期间发生了 4 例死亡；均被认为与治疗无关。一名受试者在研究结束后 13 个月死亡。从转换/滴定阶段开始到结束，84%的受试者平均疼痛评分有临床意义的改善（≥30%改善），并且平均疼痛评分在维持阶段保持稳定。
这种单一实体、缓释氢可酮制剂通常是安全的，耐受性良好，能有效减轻慢性疼痛达 48 周。这种制剂为慢性疼痛患者提供了一种新的选择，特别是那些正在服用即释氢可酮并因乙酰氨基酚而担心肝毒性的患者。
