• Jeffrey Gudin, Richard Rauck, Charles Argoff, Eva Agaiby, Joseph Gimbel, Nathaniel Katz, Stephen K Doberstein, Mary Tagliaferri, Margit Tagliaferri, Jeffrey Potts, James Wild, Lin Lu, Suresh Siddhanti, Martin Hale, and John Markman.
• *Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, New Jersey.
• Pain Med. 2020 Nov 7; 21 (7): 1347-1356.

ObjectiveTo 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).DesignUncontrolled, 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).SettingMulticenter, long-term clinical research study.MethodsNKTR-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).ResultsThe 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.ConclusionsThe study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.© 2019 American Academy of Pain Medicine.

18 keywords...

hide…