Naldemedine improves opioid-induced constipation in patients with chronic noncancer pain

SAN DIEGO — Two phase 3 trials confirmed the safety and efficacy of naldemedine for the treatment of opioid-induced constipation in patients with chronic noncancer pain, according to a presenter at DDW 2016.

Naldemedine (Shionogi) is an oral, peripherally acting mu-opioid receptor antagonist being investigated for the treatment of opioid-induced constipation.

“The medicine can be taken with or without food, which sets it apart from other products in its class at this time, and which is a concern with patient compliance,” Martin E. Hale, MD, from Gold Coast Research, said during his presentation.

Hale and colleagues performed two identical double blind, randomized, placebo-controlled trials — the COMPOSE I and II trials — in which adults assigned opioids for chronic noncancer pain received either daily 0.2 mg naldemedine or placebo for 12 weeks. All patients took opioids for at least 3 months, were on a stable dose for at least 1 month and were not taking laxatives.

In the first study, researchers randomly assigned 274 patients to naldemedine and 273 to placebo, and in the second study, 277 patients received naldemedine and 276 received placebo. Patients kept stool diaries throughout the study period.

The primary outcome was the proportion of responders, with responders defined as having at least 9 positive-response weeks overall and 3 out of the last 4 weeks. Positive-response weeks were defined as having at least three spontaneous bowel movements per week and at least one per week increased from baseline. The researchers also assessed safety and tolerability.

There were significantly greater proportions of responders in the naldemedine groups in both trials: 47.6% vs. 34.6% in the first (P = .002) and 52.5% vs. 33.5% in the second (P < .0001).

Compared with placebo, frequency of spontaneous bowel movements per week increased significantly by week 1 in the naldemedine groups, and this remained stable throughout the study period. Naldemedine-treated patients also experienced greater increases in frequency of complete spontaneous bowel movements and spontaneous bowel movements without straining from baseline to the last 2 weeks of the study period.

Treatment-emergent adverse events were comparable between groups, and the most common adverse events related to naldemedine were abdominal pain and diarrhea. Naldemedine was also not associated with signs or symptoms of opioid withdrawal, and it did not affect the analgesic effect of opioids.

“Overall the consistent results of these two studies demonstrate that once daily oral naldemedine 0.2 mg was effective in treating [opioid-induced constipation] sufferers with chronic noncancer pain and was generally well tolerated,” Hale concluded. – by Adam Leitenberger

Reference:

Hale ME, et al. Abstract #598. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego.

Disclosures: Hale reports consulting and research support from Shionogi. Please see the DDW disclosure list for all other researchers’ relevant financial disclosures.