학술논문
Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator.
Document Type
Article
Author
Shinkai, Masaharu; Katsumata, Noriyuki; Kawai, Shinichi; Kuyama, Shoichi; Sasaki, Osamu; Yanagita, Yasuhiro; Yoshida, Minoru; Uneda, Shima; Tsuji, Yasushi; Harada, Hidenori; Nishida, Yasunori; Sakamoto, Yasuhiro; Himeji, Daisuke; Arioka, Hitoshi; Sato, Kazuhiro; Katsuki, Ryo; Shomura, Hiroki; Nakano, Hideshi; Ohtani, Hideaki; Sasaki, Kazutaka
Source
Subject
Language
ISSN
0941-4355
Abstract
Purpose: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. Methods: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. Results: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6–82.7 mm). In the full analysis set, the adjusted mean change in VAS was − 22.07 and − 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was − 2.99 mm (95% confidence interval [CI] − 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. Conclusion: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. Clinical trial registration: JapicCTI-184143/jRCT2080224082 (October 5, 2018). [ABSTRACT FROM AUTHOR]