학술논문
SUMMIT-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain.
Document Type
Academic Journal
Author
Markman J; Department of Neurosurgery, Translational Pain Research Program, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.; Gudin J; Pain Management and Palliative Care Center, Englewood Hospital and Medical Center, Englewood, NJ, United States.; Rauck R; Carolinas Pain Institute, The Center for Clinical Research, Winston-Salem, NC, United States.; Argoff C; Department of Neurology, Albany Medical Center, Albany, NY, United States.; Rowbotham M; Sutter Health, CPMC Research Institute, San Francisco, CA, United States.; Agaiby E; Clinical Investigation Specialists Inc, Kenosha, WI, United States.; Gimbel J; Arizona Research Center, Phoenix, AZ, United States.; Katz N; Tufts University School of Medicine, Department of Anesthesia, Boston, MA, United States.; Doberstein SK; Nektar Therapeutics, San Francisco, CA, United States.; Tagliaferri M; Nektar Therapeutics, San Francisco, CA, United States.; Lu L; Nektar Therapeutics, San Francisco, CA, United States.; Siddhanti S; Nektar Therapeutics, San Francisco, CA, United States.; Hale M; Gold Coast Research, LLC, Plantation, FL, United States.
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7508686 Publication Model: Print Cited Medium: Internet ISSN: 1872-6623 (Electronic) Linking ISSN: 03043959 NLM ISO Abbreviation: Pain Subsets: MEDLINE
Subject
Language
English
Abstract
NKTR-181, a new molecular entity, mu-opioid receptor agonist with an inherently slow rate of central nervous system (CNS) entry, was designed to provide analgesia while reducing abuse potential. This phase 3, enriched-enrollment, randomized-withdrawal trial evaluated the analgesic efficacy, safety, and tolerability of NKTR-181 in patients with chronic low-back pain (CLBP). Adults with moderate-to-severe CLBP refractory to nonopioid analgesics achieving an analgesic NKTR-181 dosage (100-400 mg twice daily) during the open-label titration period were randomized to continued NKTR-181 treatment, double-blind, or switched to placebo. The study was conducted at 55 sites in the United States. Of 1189 patients exposed to NKTR-181 during the titration period, 610 were randomized to NKTR-181 100 to 400 mg every 12 hours or placebo for 12 weeks. The primary outcome measure was change in weekly pain score (scale, 0-10) at 12 weeks from randomization baseline. Secondary outcome measures included responder rates defined by ≥30% and ≥50% improvement in pain score from screening to 12 weeks. Among 610 randomized patients, the mean pain score decreased from 6.73 to 2.32 during open-label titration. After randomization, the least-squares mean change in pain score was +0.92 for NKTR-181 vs +1.46 for placebo (P = 0.002). The ≥30%-improvement responder rate of NKTR-181 vs placebo was 71.2% vs 57.1% (P < 0.001), and the ≥50%-improvement responder rate was 51.1% vs 37.9% (P = 0.001). NKTR-181 was well tolerated with a low incidence (<3%) of CNS-related adverse events during the randomized treatment phase. In patients with moderate-to-severe CLBP, NKTR-181 demonstrated significant analgesic efficacy and a favorable safety/tolerability profile, with a low incidence of CNS adverse events.