Preventive effect of naldemedine for opioid-induced constipation in patients with cancer starting opioids: A multicenter, double-blinded, randomized, placebo-controlled, phase 3 trial.

LBA12014 Background: A peripherally acting μ-opioid receptor antagonist (PAMORA), such as naldemedine, could alleviate OIC in cancer patients. However, the evidence of PAMORA on OIC prevention in cancer patients starting opioid analgesia is limited. This clinical trial aimed to confirm the preventive effect of naldemedine for OIC in cancer patients who start daily strong opioid administration compared with placebo. Methods: We conducted a multicenter, double-blinded, randomized, placebo-controlled trial between July 2021 and May 2023 with four academic hospital in Japan (jRCTs031200397). Patients with cancer starting regular strong opioid for the first time for cancer pain, and age 20 years or older were included. The eligible patient was randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio. The protocol treatment period was 14 days after the start of naldemedine (or placebo) and the naldemedine group had Symproic at 0.2 mg once a day after breakfast for 14 days. The placebo group had the placebo once a day after breakfast for 14 days. The primary endpoint was the proportion of patients with a Bowel Function Index (BFI) of less than 28.8 on Day 14. We conducted the safety assessments with the number of all adverse events occurring during the protocol treatment period using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Japanese translation of Japan Clinical Oncology Group. Results: Of the 103 patients were assessed for eligibility, 99 patients were randomly assigned on a 1:1 basis to receive naldemedine (n = 49) or placebo (n = 50). The BFI score at Day 1 was 18.3±19.8 with naldemedine group and 18.2±20.0 with placebo. The proportion of patients with a BFI of less than 28.8 on Day 14 was significantly greater with naldemedine group (64.6% [31 of 48 patients]; 95% CI, 51.1% to 78.1%) than with placebo (17.0% [8 of 47 patients]; 95% CI, 6.3% to 27.8%) with a difference of 47.6% (95% CI, 30.3% to 64.8%, p< 0.0001). There was no statistical difference in the proportion of adverse events; abdominal distention, abdominal pain, diarrhea, bowel obstruction, and nausea. However, there was a significantly lower proportion of vomiting in patients treated with naldemedine. During the treatment period, none of patients treated with naldemedine had diarrhea, nausea, or vomiting as adverse events causally related to protocol treatment (0.0% [0 of 48 patients] v.s 34.0% [16 of 47 patients]. Conclusions: Naldemedine is a valuable option with proven efficacy in preventing OIC in cancer patients starting regular strong opioids. Clinical trial information: 031200397 .