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). Issue 7 (30th July 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Pain medicine. Volume 21:Issue 7(2020)
• Page Start: 1347
• Page End: 1356
• Publication Date: 2019-07-30
• Subjects: NKTR-181 -- Chronic Noncancer Pain -- SUMMIT-08 -- Long-term Safety -- Opioids -- Chronic Pain -- Low Back Pain -- Oxycodegol; Pain -- Periodicals; Pain -- Treatment -- Periodicals; Analgesics -- Periodicals; Pain -- Periodicals; Pain Management -- Periodicals; Douleur -- Périodiques; Douleur -- Traitement -- Périodiques; Analgésiques -- Périodiques; Analgésique; Soulagement de la douleur; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.047205
• DOI: 10.1093/pm/pnz169
• Languages: English
• ISSNs: 1526-2375

Abstract

Abstract: Objective: 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). Design: 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). Setting: Multicenter, long-term clinical research study. Methods: 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). Results: 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. Conclusions: The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.