Treatment of opioid-induced constipation with naldemedine in patients with cancer: onset of action in a randomized phase 3 trial

Background

Opioid analgesics are widely administered to treat patients with cancer pain; however, many patients suffer from opioid-induced constipation (OIC) as a side effect. Naldemedine (NAL), a peripherally-acting &mgr;-opioid receptor antagonist (PAMORA), is being developed for the treatment of patients with OIC. The aim of this analysis was to assess the onset of action of NAL in the context of primary efficacy and safety results previously reported.

Methods

The study was a double-blind, randomized, placebo-controlled phase 3 trial in Japan. Cancer patients with OIC, defined as having ≤ 5 spontaneous bowel movements (SBMs) during the 2-week qualification period, were evenly assigned to either oral NAL 0.2 mg QD or placebo (PBO). The primary efficacy endpoint was SBM responder rate (percentage of patients with ≥ 3 SBMs/week and an increase from baseline of ≥ 1 SBM/week) during the 2-week treatment period. To assess the onset of action, 1) time to the first SBM, 2) proportion of patients with at least 1 SBM at several time points after initial dose and 3) change in frequency of SBMs/week from baseline to first week were evaluated.

Results

A total of 193 patients were randomized (NAL: 97, PBO: 96). The SBM responder rate of NAL was significantly larger than that of PBO (71.1% vs 34.4%, respectively; P 

Conclusions

Treatment with NAL led to timely improvement of OIC in patients with cancer and was generally well tolerated.

Clinical trial identification

JapicCTI-132340, 15 November 2013

Legal entity responsible for the study

Shionogi & Co., Ltd.

Funding

Shionogi & Co., Ltd.

Disclosure

N. Katakami: Speakers Bureau Dainippon Sumitomo, Chugai, Boehringer, AZ, Lilly, Taiho, Janssen, Novartis, Pfizer, Ono, Daiichi Sankyo Research Fund AZ, Eisai, Ono, Kyowa Hakko Kirin, Shionogi, Daiichi Sankyo, Taiho, Chugai, Lilly, Boehringer, Merck Serono. T. Harada: Honoraria Chugai Pharma, Taiho Pharmaceutical, Ono Pharmaceutical, AstraZeneca KK, Novartis, Boehringer Ingelheim. K. Shinozaki: Honoraria Takeda, Merck Serono, GSK, AstrZeneca, Novartis, Chugai, Daiichi Sankyo, Mochida, Taiho, Ono, Otsuka, Yakult. T. Yokota, M. Arai, Y. Suzuki: Employee of Shionogi and have stock of Shionogi. N. Boku: Honoraria Taiho, Merck Senoro, Ono, Shionogi, Chugai, Yakult, Daiichi Sankyo, Lilly, Takeda Research Funding Taiho, Chugai. All other authors have declared no conflicts of interest.