S 297995 (naldemedine) meets primary endpoint in a phase III study for opioid-induced constipation- Shionogi

Once-daily S 297995 (naldemedine), from Shionogi, met its primary and secondary endpoints in a phase III study (COMPOSE II) for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. This is the third Phase III trial in which naldemedine met its primary and key secondary endpoints. COMPOSE II is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The study was designed to evaluate the efficacy and safety of naldemedine therapy, versus placebo, in 553 patients receiving chronic opioid therapy for at least three months, and who experience OIC accompanied by chronic non-cancer pain.

Study results showed that a 0.2 mg tablet of naldemedine given once daily significantly improved the frequency of spontaneous bowel movement (SBM) compared with placebo over 12 weeks. Naldemedine was generally well-tolerated with the most commonly reported side effects being gastrointestinal disorders.

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).