학술논문
Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.
Document Type
Academic Journal
Author
Henningfield JE; Pinney Associates, Bethesda, Maryland.; Gudin J; Englewood Hospital and Medical Center, Englewood, New Jersey.; Rauck R; Carolinas Pain Institute and The Center for Clinical Research, Winston-Salem, North Carolina.; Gimbel J; Arizona Research Center, Phoenix, Arizona.; Tagliaferri M; Nektar Therapeutics, San Francisco, California.; Doberstein SK; Nektar Therapeutics, San Francisco, California.; Di Fonzo C; Nektar Therapeutics, San Francisco, California.; Lu L; Nektar Therapeutics, San Francisco, California.; Katz N; Tufts University School of Medicine, Boston, Massachusetts.; Analgesic Solutions, Wayland, Massachusetts, USA.; Siddhanti S; Nektar Therapeutics, San Francisco, California.; Schnoll S; Pinney Associates, Bethesda, Maryland.
Source
Publisher: published by Oxford University Press on behalf of the American Academy of Pain Medicine Country of Publication: England NLM ID: 100894201 Publication Model: Print Cited Medium: Internet ISSN: 1526-4637 (Electronic) Linking ISSN: 15262375 NLM ISO Abbreviation: Pain Med Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.
Design: Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).
Setting: Conducted in the United States at multiple sites.
Methods: SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.
Results: Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).
Conclusions: NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.
(© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)
Design: Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).
Setting: Conducted in the United States at multiple sites.
Methods: SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.
Results: Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).
Conclusions: NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.
(© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)