Efficacy and safety of controlled-release oxycodone for the management of moderate-to-severe chronic low back pain in Japan: results of an enriched enrollment randomized withdrawal study followed by an open-label extension study
Received 4 July 2018
Accepted for publication 10 December 2018
Published 17 January 2019 Volume 2019:12 Pages 363—375
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Michael A Überall
Mikito Kawamata,1 Masako Iseki,2 Mamoru Kawakami,3 Shoji Yabuki,4 Takuma Sasaki,5 Mitsuhiro Ishida,5 Atsushi Nishiyori,5 Hideaki Hida,6 Shin-ichi Kikuchi4
1Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan; 2Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 3Spine Care Center, Wakayama Medical University Kihoku Hospital, Wakayama, Japan; 4Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan; 5Clinical Development Department, Shionogi & Co. Ltd., Osaka, Japan; 6Biostatistics Center, Shionogi & Co. Ltd., Osaka, Japan
Background: Oxycodone is one of the options for the management of CLBP in patients with an inadequate response to other analgesics. However, oxycodone is not yet approved for noncancer pain in Japan. Here, we assessed the efficacy and long-term safety of S-8117, a controlled-release oxycodone formulation, for the management of Japanese CLBP patients.
Patients and methods: An initial enriched enrollment randomized withdrawal, double-blind, placebo-controlled, 5-week phase III trial was conducted across 54 centers in Japan to assess the efficacy of S-8117 vs placebo in moderate-to-severe CLBP patients. Subsequently, a 52-week, open-label, single-arm study was conducted across 53 centers in Japan to evaluate the long-term safety of S-8117. The primary endpoint was the time to inadequate analgesic response during 35 days of the double-blind period. Secondary endpoints were the percentages of patients with inadequate analgesic response, discontinuation rate due to inadequate analgesic effects or AEs, and changes in scores of BPI severity, BPI pain interference, SF-36, and Roland-Morris Disability Questionnaire. Safety was assessed as the incidence of AEs and ADRs.
Results: Of the 189 patients enrolled in the double-blind study, 130 patients who completed the initial titration period were randomized 1:1 to receive either S-8117 (n=62) or placebo (n=68). Baseline characteristics were comparable across the study groups. The time to inadequate analgesic response was significantly longer in patients treated with S-8117 than placebo (P=0.0095). Secondary endpoints corroborated the efficacy of S-8117 vs placebo. Overall, 478 AEs were reported in 73/75 patients in the long-term study. The most frequent ADRs were somnolence, constipation, and nausea. No case of drug dependence was reported in the long-term study.
Conclusion: Short-term efficacy vs placebo and long-term safety of S-8117 were demonstrated for the management of Japanese patients with moderate-to-severe CLBP.
Keywords: chronic low back pain, opioids, oxycodone, RCT
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