<p>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</p>

Abstract

BackgroundOxycodone 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 methodsAn 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.ResultsOf 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.ConclusionShort-term efficacy vs placebo and long-term safety of S-8117 were demonstrated for the management of Japanese patients with moderate-to-severe CLBP.

Opioids for chronic low back pain: An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks of double‐blind duration

“…We included thus eight nine studies (Christoph, Eerdekens, Kok, Volkers, & Freynhagen, 2017;Gimbel et al, 2016;Hale, Zimmerman, Eyal, & Malamut, 2015;Kawamata et al, 2019;Rauck et al, 2015;Rauck et al, 2014;Rauck, Potts, Xiang, Tzanis, & Finn, 2016;Wen, Sitar, Lynch, He, & Ripa, 2015) with 2,980 participants and a total of 21 studies with 7,650 participants into the qualitative and quantitative analyses (see Figure 1).…”

“…Hale et al (2015) reported diversion in 12 out of 623 (1.9%) participants and loss of study drugs in 20 out of 623 (3.2%) participants. Kawamata et al (2019) used two validated questionnaires and found no signals indicative of abuse or addiction. Steiner et al (2011) did not report on their methods of assessment and stated that no patients were suspected of abuse of buprenorphine.…”

Efficacy and harms of long‐term opioid therapy in chronic non‐cancer pain: Systematic review and meta‐analysis of open‐label extension trials with a study duration ≥26 weeks

“…No aberrant drug behaviour was reported in the Japanese study analysed (Kawamata et al, ). No opioid crisis has been reported in Japan (Onishi et al, ).…”

“…The updated searches (last performed June 16, 2019) produced 90 hits after duplicates were removed. We included four new studies with 1,154 participants (Blagden, Hafer, Duerr, Hopp, & Bosse, 2014;Hale, Zimmerman, Ma, and Malamut 2015;Hale, Urdaneta, Kirby, Xiang, & Rauck, 2017;Kawamata et al, 2019) and a total of 15 studies with 3,590 participants into the qualitative and quantitative analysis (see Figure 1).…”

Safety of tapentadol compared with other opioids in chronic pain treatment: network meta-analysis of randomized controlled and withdrawal trials

“…Of the ten trials applying efficacy criteria, one of the trials (58) used patient defined criteria, asking patients "has this treatment helped your pain enough so that you would continue to take this medication?" Six of the 11 trials also assessed patients for safety (53)(54)(55)(60)(61)(62). Each of these trials only put patients forward for randomization if they experienced no, or tolerable adverse events.…”