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)

  • Pain Med. 2020 Nov 7;21(7):1347-1356. doi: 10.1093/pm/pnz169.
Jeffrey Gudin  1  2 ,  Richard Rauck  3 ,  Charles Argoff  4 ,  Eva Agaiby  5 ,  Joseph Gimbel  6 ,  Nathaniel Katz  7  8 ,  Stephen K Doberstein  9 ,  Mary Tagliaferri  9 ,  Margit Tagliaferri  9 ,  Jeffrey Potts  10 ,  James Wild  11 ,  Lin Lu  9 ,  Suresh Siddhanti  9 ,  Martin Hale  12 ,  John Markman  13
Affiliations
  • 1. *Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, New Jersey.
  • 2. Pain Management and Wellness Center, Englewood, New Jersey.
  • 3. Carolinas Pain Institute and The Center for Clinical Research, Winston-Salem, North Carolina.
  • 4. Department of Neurology, Albany Medical Center, Albany, New York.
  • 5. Clinical Investigation Specialists Inc, Kenosha, Wisconsin.
  • 6. Arizona Research Center, Phoenix, Arizona.
  • 7. Tufts University School of Medicine, Boston, Massachusetts.
  • 8. **Analgesic Solutions, Wayland, Massachusetts.
  • 9. Nektar Therapeutics, San Francisco, California.
  • 10. Great Lakes Research Group, Inc, Bay City, Michigan.
  • 11. Upstate Clinical Research Associates, Williamsville, New York.
  • 12. Gold Coast Research, LLC, Plantation, Florida.
  • 13. Department of Neurosurgery, Translational Pain Research Program, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
PMID: 31361019 DOI: 10.1093/pm/pnz169
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.

Keywords
Chronic Noncancer Pain; Chronic Pain; Long-term Safety; Low Back Pain; NKTR-181; Opioids; Oxycodegol; SUMMIT-08.
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