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

Naldemedine, an oral, peripherally acting mu-opioid receptor antagonist in development for the treatment of opioid-induced constipation, showed significant benefit vs. placebo in a phase 3 study of patients with chronic noncancer pain, according to a press release.

Data from the COMPOSE I study, which was presented last week at the American Academy of Pain Medicine 2016 Annual Meeting, also showed naldemedine (Shionogi) was generally well tolerated and had a low incidence of gastrointestinal side effects.

“The millions of patients on chronic opioid therapy often suffer from constipation, which can be extremely debilitating and may lead to non-adherence and improper use of pain medications,” Juan Camilo Arjona Ferreira, MD, Shionogi’s senior vice president of clinical development, said in the press release. “We are very encouraged by the naldemedine study results, both in terms of its effect in treating OIC and its safety profile.”

In the multicenter, double-blind study, 547 patients on opioid therapy for at least 3 months (with a stable dose for at least 4 weeks) for chronic noncancer pain, who also had OIC, were randomly assigned to receive a 0.2 mg naldemedine tablet or placebo once daily for 12 weeks. Responder rate, defined as at least 9 positive response weeks total and 3 positive response weeks out of the last 4 weeks of treatment, served as the primary endpoint. A positive response week was defined as at least three spontaneous bowel movements per week and an increase of at least one spontaneous bowel movement per week from baseline.

Overall, 47.6% of the treatment group achieved the primary endpoint vs. 34.6% of the placebo group. Naldemedine also significantly improved all key secondary endpoints including increased complete spontaneous bowel movements per week, and increased spontaneous bowel movements without straining per week, from baseline to the last 2 weeks vs. placebo.

Abdominal pain and diarrhea occurred in 6.3% vs. 1.8% and 6.6% vs. 2.9% of the treatment and placebo groups, respectively.

The COMPOSE I study is one of seven clinical studies being conducted as part of the global COMPOSE development program, involving both cancer and chronic noncancer pain patients with OIC. Previously, naldemedine also met its primary and key secondary endpoints in the COMPOSE II and IV trials in chronic noncancer pain patients and cancer patients, respectively.

Disclosures: Ferreira is an employee of Shionogi.