Dataset Information

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.

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).

SUBMITTER: Shinkai M

PROVIDER: S-EPMC10756890 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Shinkai Masaharu M Katsumata Noriyuki N Kawai Shinichi S Kuyama Shoichi S Sasaki Osamu O Yanagita Yasuhiro Y Yoshida Minoru M Uneda Shima S Tsuji Yasushi Y Harada Hidenori H Nishida Yasunori Y Sakamoto Yasuhiro Y Himeji Daisuke D Arioka Hitoshi H Sato Kazuhiro K Katsuki Ryo R Shomura Hiroki H Nakano Hideshi H Ohtani Hideaki H Sasaki Kazutaka K Adachi Takeshi T

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20231229 1

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 38157081

Similar Datasets

Project description:Background and objectivesKnee osteoarthritis pain is a chronic form of pain for which conventional non-steroidal anti-inflammatory drugs may provide insufficient analgesia. Twice-daily tramadol hydrochloride (65% sustained-release/35% immediate-release) bilayer tablets are a novel formulation of tramadol developed for managing chronic pain. The objectives of this study were to examine the effectiveness and safety of this formulation in patients with chronic knee osteoarthritis pain.MethodsThis was a multicenter, randomized, placebo-controlled, double-blind, parallel-group, treatment-withdrawal study. Patients with a reduction in Numeric Rating Scale (NRS) for pain of ≥2 points during a 1-3-week, open-label, tramadol dose-escalation period (100-300 mg/day) were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients with inadequate efficacy (increase in NRS ≥2 points/patient request) were withdrawn. Outcomes included the time to inadequate analgesic efficacy from randomization (primary endpoint), the cumulative retention rate, and safety.ResultsOverall, 249 and 160 patients entered the dose-escalation and double-blind periods, respectively (tramadol 79; placebo 81). Kaplan-Meier analysis revealed superiority of tramadol (log-rank p = 0.042), and a hazard ratio of 0.50 (95% confidence interval [CI] 0.25-0.99). Documentation of an inadequate analgesic effect was less frequent in the tramadol group (15.4%, 95% CI 8.2-25.3% vs. 30.9%, 95% CI 21.1-42.1%). The cumulative retention rate was greater in the tramadol group (83.7% vs. 69.0%). Adverse events occurred in 80.6% (200/248) of patients in the open-label period, and in 38.5% (30/78) and 13.6% (11/81) of patients in the tramadol and placebo groups, respectively, in the double-blind period. Opioid-associated adverse events, such as nausea, vomiting, constipation, somnolence, and dizziness, were the most frequent events.ConclusionThis study demonstrated the analgesic efficacy and safety of sustained-release tramadol tablets with an immediate-release component for chronic knee osteoarthritis pain.Trial registrationJapicCTI-132103 (Japan Pharmaceutical Information Center; registration date February 25, 2015).

Dataset Information

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.

Purpose

Methods

Results

Conclusion

Clinical trial registration

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets