![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Background
In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.
Subjects and methods
This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment.
Results
The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics.
Conclusion
The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.
Supplementary material
Hirosaki National Hospital
Mito Red Cross Hospital
Mito Medical Center
Yuai Memorial Hospital
Ibaraki Prefectural Central Hospital
Tsuchiura Kyodo General Hospital
Tsukuba Medical Center Hospital
Tochigi Cancer Center
Gunma Prefectural Cancer Center
Takasaki General Medical Center
Ageo Central General Hospital
National Hospital Organization Saitama National Hospital
National Hospital Organization Chiba Medical Center
Chiba Cancer Center
Funabashi Municipal Medical Center
Chiba Tokushukai Hospital
Kanto Central Hospital of the Mutual Aid Association of Public School Teachers
Tokyo Metropolitan Health and Medical Treatment Corporation Toshima Hospital
Kanagawa Cancer Center
Kawasaki Municipal Hospital
Shonan Kamakura General Hospital
Aizawa Hospital
Japanese Red Cross Society Suwa Hospital, Suwa Red Cross Hospital
Japanese Red Cross Shizuoka Hospital
Yaizu City Hospital
Shizuoka Prefectural Hospital Organization, Shizuoka General Hospital
Shizuoka Cancer Center
Aichi Cancer Center Hospital
Toyohashi Medical Center
Matsusaka City Hospital
Kyoto Okamoto Memorial Hospital
Osaka General Medical Center
Rinku General Medical Center
National Hospital Organization Kinki-Chuo Chest Medical Center
Saiseikai Noe Hospital
Sano Hospital
Meiwa Hospital
Japanese Red Cross Society Himeji Hospital
Institute of Biomedical Research and Innovation Hospital
Okayama Medical Center
National Hospital Organization Kure Medical Center and Chugoku Cancer Center
Iwakuni Clinical Center
Japan Community Health Care Organization, Shimonoseki Medical Center
Saiseikai Imabari Hospital
Ehime Prefectural Central Hospital
Saiseikai Fukuoka General Hospital
Japan Community Health Care Organization, Kyushu Hospital
Beppu Medical Center
Miyazaki Prefectural Miyazaki Hospital
Acknowledgments
This study and preparation of this report were funded by Daiichi Sankyo Co Ltd. The authors wish to thank all of the investigators at the participating centers (see Box S1) for their contribution to this study. We would also like to thank Marion Barnett of Edanz Medical Writing for providing editorial support.
Disclosure
SI, AI, and YK are employees of Daiichi Sankyo. YS participated in this study as a medical specialist, and ST and EA functioned as safety assessment advisors. YS has received personal fees from Daiichi Sankyo. The authors report no other conflicts of interest in this work.