Open AccessSUMMIT-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain
Author(s) -
John D. Markman,
Jeffrey Gudin,
Richard Rauck,
Charles E. Argoff,
Michael C. Rowbotham,
Eva Agaiby,
Joseph Gimbel,
Nathaniel Katz,
Stephen K. Doberstein,
Mary Tagliaferri,
Li Lin,
Suresh Siddhanti,
Martin Hale
Publication year - 2019
Publication title -
pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.524
H-Index - 258
eISSN - 1872-6623
pISSN - 0304-3959
DOI - 10.1097/j.pain.0000000000001517
Subject(s) - tolerability , medicine , placebo , randomization , analgesic , randomized controlled trial , anesthesia , opioid , adverse effect , alternative medicine , receptor , pathology
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.