Gudin Jeffrey, Rauck Richard, Argoff Charles, Agaiby Eva, Gimbel Joseph, Katz Nathaniel, Doberstein Stephen K, Tagliaferri Mary, Tagliaferri Margit, Potts Jeffrey, Wild James, Lu Lin, Siddhanti Suresh, Hale Martin, Markman John
*Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, New Jersey.
Pain Management and Wellness Center, Englewood, New Jersey.
Pain Med. 2020 Nov 7;21(7):1347-1356. doi: 10.1093/pm/pnz169.
To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).
Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).
Multicenter, long-term clinical research study.
NKTR-181 administered at doses of 100-600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF).
The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.
The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.
评估新型μ-阿片受体激动剂NKTR-181在中度至重度慢性下腰痛（CLBP）或其他慢性非癌性疼痛（CNP）患者中的长期安全性，该激动剂可能具有较低的人类滥用潜力。
对NKTR-181进行的非对照、多中心、开放标签长期研究，包括三个阶段：筛查（≤21天）、治疗（52周）和安全性随访（末次剂量的NKTR-181后约14天）。
多中心长期临床研究。
在未使用过阿片类药物和有阿片类药物使用经验的患者中，评估每日两次（BID）剂量为100 - 600 mg的NKTR-181。患者为初治患者或在完成随机、安慰剂对照的3期疗效研究（SUMMIT-07）后入组。安全性评估包括不良事件记录、阿片类药物戒断测量和临床实验室检查。使用改良的简明疼痛量表简表（mBPI-SF）评估有效性。
该研究纳入了638例患者。最常报告的治疗中出现的不良事件（TEAE）为便秘（26%）和恶心（12%）。5%的患者报告了严重TEAE，研究者认为这些与NKTR-181无关。没有死亡病例或呼吸抑制报告病例。在整个治疗过程中，观察到从基线到研究结束时mBPI-SF疼痛强度和疼痛干扰持续降低。仅2%的患者因缺乏疗效而停用NKTR-181，11%的患者因治疗相关不良事件而停用。高达600 mg BID的NKTR-181剂量总体耐受性良好，患者发生阿片类药物相关不良事件的发生率较低。
研究结果支持NKTR-181是中度至重度CLBP或CNP患者的安全有效选择这一前提。
