Interim analysis of a prospective, multicenter, clinical trial of oxycodone naloxone prolonged-release tablets for severe cancer pain complicated with opioid-induced constipation

Zhonghua Yi Xue Za Zhi. 2026 Jul 21;106(26):2723-2729. doi: 10.3760/cma.j.cn112137-20260325-00807.

ABSTRACT

Objective: To evaluate the effects of oxycodone naloxone prolonged-release tablets on bowel function, analgesic control, quality of life, and safety in patients with severe cancer pain and opioid-induced constipation (OIC).

Methods: This study is an interim analysis of a prospective, multicenter, single-arm trial. Patients with severe cancer pain and OIC from nine medical institutions in China between April 2025 and January 2026 were enrolled and treated with oxycodone naloxone prolonged-release tablets for 4 weeks. The primary endpoint was bowel function improvement assessed by the Bowel Function Index (BFI). Secondary endpoints included analgesic effect (Brief Pain Inventory-Short Form, BPI-SF), defecation status (Complete Spontaneous Bowel Movement, CSBM), quality of life (Patient Assessment of Constipation Quality of Life, PAC-QOL), and safety (adverse events). One-way repeated measures analysis of variance was used to compare the above measures between different post-treatment time points and baseline. The Lan-DeMets α-spending function (with O'Brien-Fleming adjustment) was applied to adjust the α level for the interim analysis, yielding an interim analysis boundary value of 0.000 6 (two-sided) and a final analysis boundary value of 0.049 8.

Results: Planned enrollment was 203 patients; by January 2026, 78 patients were actually enrolled. The modified full analysis set (mFAS) comprised 64 patients, and the safety analysis set (SAS) comprised 77 patients. In the mFAS group, BFI scores decreased significantly after treatment (F=36.39, P<0.001). The change from baseline in BFI score at week 4 was -26.7 (-39.2, -10.0) points (P<0.001). BPI-SF scores at all post-treatment time points were lower than baseline, and CSBM at all time points increased compared with baseline, and the PAC-QOL score at all time points decreased compared with baseline (all P<0.001). In the SAS group, the daily opioid dose was [M(Q₁, Q₃)] 40.0 (20.0, 65.5) mg. The overall incidence of adverse events was 54.5% (42/77), with the most common being nausea (15.6%, 12/77) and vomiting (14.3%, 11/77). The incidence of serious adverse events was 6.5% (5/77).

Conclusion: Oxycodone naloxone prolonged-release tablets improve bowel function and defecation in Chinese patients with severe cancer pain and OIC, do not compromise analgesic effect, enhance constipation-related quality of life, and demonstrate acceptable safety.

PMID:42477942 | DOI:10.3760/cma.j.cn112137-20260325-00807