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Naldemedine relieves opioid-induced constipation within 4 hours
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LAS VEGAS — Naldemedine induced spontaneous bowel movements more quickly than placebo — often within 4 hours of first dose — and maintained its efficacy for 12 weeks, according to data presented at ACG 2016.
“In two phase 3 studies, naldemedine was effective as a treatment for opioid-induced constipation in subjects with chronic non-cancer pain,” James Wild, MD, of Upstate Clinical Research Associates, said during his presentation. “The onset of action of naldemedine was timely, with more subjects experiencing a spontaneous bowel movement or a complete spontaneous bowel movement within 4 to 24 hours after the initial dose compared with placebo.”
Naldemedine (S-297995, Shionogi) is a peripherally-acting µ-opioid receptor agonist designed to be taken once daily by adults with opioid-induced constipation, Wild said.
COMPOSE-1 and COMPOSE-2 included people aged 18 to 80 years with chronic non-cancer pain for at least 3 months and receiving at least 30 mg per day of morphine equivalents for at least 1 month. Participants were not using laxatives.
Researchers screened participants for 2 to 4 weeks and then randomly assigned the participants to either placebo (COMPOSE-1, n = 272; COMPOSE-2 n = 274) or 0.2 mg naldemedine once daily (COMPOSE-1, n = 273; COMPOSE-2 = 276) for 12 weeks with assessments at baseline, day 1 and weeks 1, 2, 4, 8 and 12. The researchers followed the participants for 4 weeks and conducted additional assessment at week 16.
In this exploratory efficacy analysis, Wild and colleagues reported the proportion of patients who had a spontaneous bowel movement (SBM) or complete SBM (CSBM) within 4 to 24 hours after initial dose of naldemedine and the time to the SBM or CSBM after the initial dose. Researchers defined responders as having 9 weeks or more of positive response and 3 weeks out of 4 weeks at the end of treatment. They defined positive response as three or more SBMs in a week.
At baseline, patients in COMPOSE-1 reported 1.3 SBMs per week in both groups while patients in COMPOSE-2 reported 1.16 SBMs in the naldemedine group and 1.17 in the placebo group.
Of those treated with naldemedine in COMPOSE-1, 47.6% responded compared with 34.6% of those taking the placebo (13% difference; 95% CI, 4.8-21.3). In COMPOSE-2, 52.5% of those treated with naldemedine had a response vs. 33.6% of those taking placebo (18.9% difference; 95% CI, 10.8-27).
“The time to first SBM or CSBM was significantly shorter with the naldemedine than placebo and the efficacy of naldemedine was maintained over the entire 12-week treatment period,” Wild said. “A lot of the benefit occurs within the first 24 hours.”
Additionally, at all time points in both studies, the proportion of participants treated with naldemedine who had one or more SBM within 24 hours of the first dose was significantly greater than the placebo-treated participants. In COMPOSE-1, within 24 hours, 61.2% of those on naldemedine had one or more SBM vs. 28.3% of the placebo group (P < .0001). In COMPOSE-2, the rates were 56.5% and 33.6%, respectively (P < .0001). Similarly, CSBM rates were 36.3% vs. 10.7% in COMPOSE-1 and 33.7% vs. 14.2% in COMPOSE-2.
Adverse event rates were similar among both studies and both groups. – by Katrina Altersitz
Reference:
Wild J, et al. Abstract #65. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 14-19, 2016; Las Vegas, NV.
Disclosure: Wild reports acting as a study investigator and reviewer of clinical study report for Shionogi.
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