Two phase III trials show efficacy of S 297995 (naldemedine) in opioid-induced constipation- Shionogi

Shionogi announced positive results from two identically-designed 12 week phase III studies (COMPOSE I and II) demonstrating consistent efficacy and safety of S 297995 (naldemedine) in treating opioid-induced constipation (OIC) in patients with chronic non-cancer pain. COMPOSE I and COMPOSE II found that, for the primary endpoint, 47.6 percent and 52.5 percent of patients taking 0.2 mg tablet of naldemedine experienced improvements in the frequency of spontaneous bowel movements (SBMs) for at least nine out of the 12 weeks, compared with 34.6 percent and 33.6 percent of patients on placebo, respectively.

Additionally, naldemedine significantly improved all secondary endpoints in both studies, which included a significant increase in the frequency of complete SBMs per week and SBMs without straining per week from baseline to the last two weeks of the study, as compared to placebo. Results also showed that naldemedine had a low incidence of gastrointestinal side effects, and did not impact the analgesic effect of opioids. Abdominal pain and diarrhea were the only treatment-emergent adverse events reported in greater than five percent of patients in the naldemedine group compared to the placebo group.

In COMPOSE I, 6.3 percent of patients on naldemedine reported abdominal pain vs. 1.8 percent on placebo; in COMPOSE II, it was 5.2 vs. 1.1 percent, respectively. Diarrhea was reported in 6.6 percent of patients on naldemedine vs. 2.9 percent on placebo in COMPOSE I; the rate was 8.9 vs. 1.8, respectively, in COMPOSE II. The data was presented during 2016 Digestive Disease Week.

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).