{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T10:23:38Z","timestamp":1763202218444},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Nektar Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (\u226421\u2009days), treatment (52\u2009weeks), and safety follow-up (\u223c14\u2009days after the last dose of NKTR-181).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Multicenter, long-term clinical research study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>NKTR-181 administered at doses of 100\u2013600\u2009mg twice daily (BID) was evaluated in opioid-na\u00efve 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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2009mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pm\/pnz169","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T03:13:56Z","timestamp":1561000436000},"page":"1347-1356","source":"Crossref","is-referenced-by-count":7,"title":["Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS)"],"prefix":"10.1093","volume":"21","author":[{"given":"Jeffrey","family":"Gudin","sequence":"first","affiliation":[{"name":"*Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, New Jersey"},{"name":"Pain Management and Wellness Center, Englewood, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Rauck","sequence":"first","affiliation":[{"name":"Carolinas Pain Institute and The Center for Clinical Research, Winston-Salem, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Argoff","sequence":"first","affiliation":[{"name":"Department of Neurology, Albany Medical Center, Albany, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Agaiby","sequence":"first","affiliation":[{"name":"Clinical Investigation Specialists Inc, Kenosha, 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