Naldemedine relieves opioid-induced constipation

Reuters Health Information: Naldemedine relieves opioid-induced constipation

Naldemedine relieves opioid-induced constipation

Last Updated: 2017-06-09

By Will Boggs MD

NEW YORK (Reuters Health) - Naldemedine is effective for treating opioid-induced constipation in patients with chronic noncancer pain, according to results from the COMPOSE-1 and COMPOSE-2 trials.

Naldemedine is a once-daily, oral, peripherally acting mu-opioid receptor antagonist (PAMORA) that was recently approved by the U.S. Food and Drug Administration for the treatment of opioid-induced constipation in adults with chronic noncancer pain.

Dr. Juan Camilo Arjona Ferreira from Shionogi, Inc., in Florham Park, New Jersey, and colleagues describe the results of the two trials that supported this approval in their new report, online May 30 in The Lancet Gastroenterology and Hepatology.

Both studies included a 12-week treatment with naldemedine or placebo administered orally once a day with or without food. The primary efficacy endpoint was the proportion of responders, defined as patients having at least three spontaneous bowel movements (SBMs) per week and an increase from baseline of at least one SBM per week for at least nine weeks out of the 12-week treatment period and at least three of the last four weeks of the 12-week treatment period.

The proportion of responders during the treatment period was significantly higher in the naldemedine group than in the placebo group in both COMPOSE-1 (47.6% vs. 34.6%) and COMPOSE-2 (52.5% vs. 33.6%).

The mean weekly frequency of SBM increased to a greater extent in the naldemedine groups (by 3.42 in COMPOSE-1 and 3.56 in COMPOSE-2) than in the placebo groups (by 2.12 and 2.16, respectively).

Rates of treatment-emergent adverse events were similar in the naldemedine groups (49% in COMPOSE-1 and 50% in COMPOSE-2) and placebo groups (45% and 48%, respectively). Treatment-related events, however, were more common with naldemedine than with placebo, principally due to higher rates of diarrhea and abdominal pain in the naldemedine groups.

In COMPOSE-1, two of 271 naldemedine patients and one of 272 placebo patients experienced opioid withdrawal. There were no reports of opioid withdrawal in COMPOSE-2.

Pain rating scores were generally stable from baseline and did not differ meaningfully between the treatment groups in either of the two studies.

The effect of naldemedine treatment on constipation-related patient outcome measures of quality of life will be reported separately, the researchers note.

“These results show consistent efficacy of naldemedine in treating opioid-induced constipation in patients with chronic non-cancer pain,” the researchers conclude. “These studies also indicate that oral naldemedine given at 0.2 mg once a day with or without food was generally well tolerated, and did not interfere with opioid analgesia, or cause symptoms of opioid withdrawal in adult patients with chronic non-cancer pain.”

Dr. Waldemar Siemens from the University of Freiburg, Germany, who coauthored an accompanying editorial, told Reuters Health by email, “Patients on laxatives were excluded which affects external validity. Reporting of all assessed outcomes is important to prevent reporting bias. Patient-reported outcomes and the patients’ burden should be assessed and reported when a side effect or a symptom is treated.”

“Naldemedine has shown biochemical efficacy by increasing bowel movement frequency,” he said. “The secondary outcomes include also patient-reported outcomes (perception of evacuation, or straining) and show a smaller effect which is, however, still in favor of naldemedine.”

“The question emerges if one PAMORA - namely methylnaltrexone, naloxegol, or naldemedine - might be superior compared with another concerning the efficacy and safety profile,” the editorial, coauthored by Dr. Gerhild Becker, also at Freiburg, notes. “Head-to-head comparisons or network meta-analysis could give a deeper insight into this question.”

Shionogi and Co. funded the study, employed three authors, and had various relationships with the rest.


Lancet Gastroenterol Hepatol 2017.

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