S 297995 (naldemedine) phase III data shows significant improvement for patients with opioid-induced constipation- Shionogi

Shionogi has announced pivotal phase III study (COMPOSE I) results showing that once-daily treatment with S 297995 (naldemedine) significantly improved opioid-induced constipation (OIC) compared to placebo in patients with chronic non-cancer pain. The data also showed that naldemedine was generally well tolerated, with a low incidence rate of gastrointestinal (GI) related side effects.

The study found that for the primary endpoint 47.6 percent of patients taking an oral, once-daily 0.2 mg tablet of naldemedine experienced an increase in the frequency of spontaneous bowel movements (SBMs) from baseline for at least nine out of 12 weeks (including three out of the last four weeks) compared with 34.6 percent of patients on placebo over 12 weeks. Additionally, naldemedine significantly improved all key secondary endpoints, which included a significant increase in complete SBMs (CSBMs) per week, as well as SBMs without straining per week, from baseline to the last two weeks of the study period, as compared to placebo.

Abdominal pain and diarrhea were the only treatment related adverse events that were reported in five percent or more of patients, with abdominal pain reported in 6.3 percent of patients on naldemedine vs. 1.8 percent on placebo, and diarrhea reported in 6.6 percent of patients on naldemedine vs. 2.9 percent on placebo. The data are being presented at the American Academy of Pain Medicine 2016 Annual Meeting in Palm Springs.

Comment: Naldemedine is an investigational, oral, peripherally acting mu-opioid receptor antagonist (PAMORA). There are currently three products for opioid-induced constipation in Phase III trials in the US. Currently on the market are Sucampo Pharmacuetical's Amitiza (lubiprostone), Daiichi Sankyo's Movantik (naloxegol) and Salix Pharmaceutical's Relistor SC (methylnaltrexone bromide).