Novel antiemetic effect of naldemedine in patients initiating opioids for cancer pain: a secondary analysis of a randomized clinical trial.

BACKGROUND

Several studies have suggested that naldemedine may reduce opioid-induced constipation (OIC) as well as opioid-induced nausea and vomiting (OINV). This study aimed to investigate prophylactic effects of naldemedine on OINV in patients initiating regular, oral, strong opioids for cancer pain.

METHODS

In this preplanned secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial investigating the preventive effects of naldemedine on OIC, eligible patients were randomized in a 1:1 ratio to receive either naldemedine 0.2 mg or placebo once daily for 14 days. The primary endpoint was the complete response (CR) rate, defined as the proportion of patients with no vomiting episodes and no use of rescue antiemetics within the first three days of opioid initiation. The secondary endpoint was the nausea and vomiting score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL).

RESULTS

Of the 103 patients, 48 and 47 patients in each group started protocol treatment, respectively. The CR rate was significantly higher in the naldemedine group than in the placebo group (81.3% vs 38.3%, P < .001). Nausea and vomiting scores on the QLQ-C15-PAL at weeks 1 and 2 were significantly better in the naldemedine group (means 7.1 and 6.4) versus placebo (means 44.6 and 35.3; both P < .001). Within the total effect of naldemedine on the QLQ-C15-PAL nausea and vomiting scores at week 2, the proportion mediated through OIC reduction was 21.9%.

CONCLUSIONS

Naldemedine may have intrinsic antiemetic potency to prevent both OIC and OINV.

TRIAL REGISTRATION: https://jrct.niph.go.jp/ (Japan Registry of Clinical Trials) Identifier: jRCTs031200397.