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Randomized Controlled Trial
. 2024 Dec 10;42(35):4206-4217.
doi: 10.1200/JCO.24.00381. Epub 2024 Sep 10.

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial

Jun Hamano  1 , Takahiro Higashibata  2 , Takaomi Kessoku  3   4   5 , Shinya Kajiura  6 , Mami Hirakawa  7 , Shunsuke Oyamada  8 , Keisuke Ariyoshi  9 , Takeshi Yamada  10 , Yoshiyuki Yamamoto  11 , Yasuyuki Takashima  12 , Kosuke Doki  13 , Masato Homma  13 , Bryan J Mathis  14 , Tsumugi Jono  3   15 , Tomoki Ogata  3 , Kosuke Tanaka  3   4 , Yuki Kasai  3 , Michihiro Iwaki  3 , Akiko Fuyuki  3   16 , Atsushi Nakajima  3 , Ryuji Hayashi  6 , Takayuki Ando  17 , Naoki Izawa  18 , Yuko Kobayashi  19 , Yoshiki Horie  18 , Tatsuya Morita  20   21
Affiliations
Randomized Controlled Trial

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial

Jun Hamano et al. J Clin Oncol. .

Erratum in

Abstract

Purpose: Opioid-induced constipation is the most frequent and non-self-limiting adverse effect of opioid analgesia, reducing adherence and interfering with pain relief. This clinical trial aimed to clarify the preventive effect of naldemedine versus placebo for constipation in patients with cancer starting regularly dosed strong opioids therapy.

Methods: This multicenter, double-blinded, randomized, placebo-controlled, confirmatory trial was conducted between July 2021 and May 2023 at four academic hospitals in Japan (Japan Registry of Clinical Trials identifier: jRCTs031200397). Patients with cancer starting a first-time regularly dosed strong opioid for cancer pain and age 20+ years were included. Eligible patients were randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio for 14 days with protocol treatment. The primary end point was the proportion of patients with a Bowel Function Index (BFI) of <28.8 on day 14. The secondary end points included frequency of spontaneous bowel movements (SBM), quality of life (QOL), and frequency of opioid-induced nausea and vomiting (OINV).

Results: Of the 103 patients assessed for eligibility, 99 received either naldemedine (n = 49) or placebo (n = 50). A BFI of <28.8 on day 14 was significantly more likely to occur in the naldemedine group (64.6%; 95% CI, 51.1 to 78.1) versus placebo (17.0%; 95% CI, 6.3 to 27.8), and the difference between groups was 47.6% (95% CI, 30.3 to 64.8; P < .0001). The frequency of SBM, QOL, and the severity of OINV were nominally significant in the naldemedine group than in the control group.

Conclusion: Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Tatsuya Morita

Speakers' Bureau: Daiichi Sankyo, Shionogi, Hisamitsu Pharmaceutical

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Trial profile.
FIG A1.
FIG A1.
Line plot of mean BFI for naldemedine group and placebo group at days 1, 7, and 14. Bar indicated the mean of BFI with 95% CI. BFI, Bowel Function Index.
See this image and copyright information in PMC

References

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