Webster Lynn, Tummala Raj, Diva Ulysses, Lappalainen Jaakko
Vice President of Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah.
Director of Clinical Research, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland.
J Opioid Manag. 2016 Nov/Dec;12(6):405-419. doi: 10.5055/jom.2016.0360.
To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain.
Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524).
Clinical investigation centers in the United States.
Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841).
Daily oral administration of naloxegol (12.5 and 25 mg) or placebo.
Adverse events (AEs), including treatment-related AEs, serious AEs, and AEs of special interest; changes from baseline to week 12 in pain scores, daily opioid dose, and symptoms and quality-of-life measurements.
No important new AEs occurred during this extension study compared with KODIAC-04. AEs occurred more frequently with naloxegol 25 mg (41.2 percent) versus naloxegol 12.5 mg (34.0 percent) and placebo (33.0 percent). Treatment-emergent AEs occurring in >5 percent of patients in either naloxegol group during the treatment period were arthralgia (25 mg; 5.2 percent) and diarrhea (12.5 mg; 5.3 percent); two reported AEs attributable to opioid withdrawal syndrome in naloxegol groups were deemed unrelated to study medication. None of the gastrointestinal serious AEs was adjudicated as bowel perforation; one patient (naloxegol 12.5 mg) had an event adjudicated as a major cardiovascular event and was unrelated to study medication. Pain scores and daily opioid dose were unchanged, and improvements in symptoms and quality-of-life observed in KODIAC-04 were maintained throughout the extension study.
Naloxegol was generally safe and well tolerated in this 12-week extension study in patients with noncancer pain and OIC.
比较纳洛西醇与安慰剂在阿片类药物引起的便秘（OIC）和非癌性疼痛患者中的长期安全性和耐受性。
为期12周的多中心、随机、双盲、平行组3期扩展研究（KODIAC - 07，NCT01395524）。
美国的临床研究中心。
确诊为OIC的成年门诊患者（N = 302），他们完成了一项为期12周的关键3期研究（KODIAC - 04，NCT01309841）。
每日口服纳洛西醇（12.5毫克和25毫克）或安慰剂。
不良事件（AE），包括与治疗相关的AE、严重AE和特别关注的AE；从基线到第12周疼痛评分、每日阿片类药物剂量以及症状和生活质量测量的变化。
与KODIAC - 04相比，在该扩展研究期间未出现重要的新AE。25毫克纳洛西醇组的AE发生率（41.2%）高于12.5毫克纳洛西醇组（34.0%）和安慰剂组（33.0%）。在治疗期间，纳洛西醇组中任何一组中发生率超过5%的治疗中出现的AE为关节痛（25毫克组；5.2%）和腹泻（12.5毫克组；5.3%）；纳洛西醇组报告的两例归因于阿片类药物戒断综合征的AE被认为与研究药物无关。没有胃肠道严重AE被判定为肠穿孔；一名患者（12.5毫克纳洛西醇组）发生了一次被判定为重大心血管事件的情况，且与研究药物无关。疼痛评分和每日阿片类药物剂量未改变，并且在整个扩展研究中维持了KODIAC - 04中观察到的症状和生活质量的改善。
在这项针对非癌性疼痛和OIC患者的12周扩展研究中，纳洛西醇总体上安全且耐受性良好。
