Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study

Darren M. Brenner, Charles E. Argoff, Susan M. Fox, Wieslaw Bochenek, Patricia DʼAstoli, Rick E. Blakesley, David S. Reasner, Christopher R. OʼDea, Brooks D. Cash

Research output: Contribution to journalArticle

Abstract

Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. The primary endpoint was change from baseline in 8-week SBM frequency rate (SBMs/week). Secondary efficacy endpoints included 6/8-week SBM 3 + 1 responders, time to first SBM, and changes from baseline in 8-week stool consistency, abdominal bloating, and straining. Additional endpoints included treatment satisfaction and adequate relief responders. In total, 254 patients were randomized: 87, 88, and 79 received linaclotide 145 µg, linaclotide 290 µg, and placebo, respectively. The mean changes from baseline in SBMs/week during the treatment period were 2.9 and 3.5 in the linaclotide 145 and 290 µg groups (P < 0.01 for both doses), respectively, vs 1.6 in the placebo group. Diarrhea, the most common AE, was generally mild, resulting in 1.1%, 5.7%, and 1.3% of patients discontinuing in the linaclotide 145 μg, linaclotide 290 μg, and placebo groups, respectively. No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores (P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain.

Original languageEnglish (US)
Pages (from-to)1027-1036
Number of pages10
JournalPain
Volume161
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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    Brenner, D. M., Argoff, C. E., Fox, S. M., Bochenek, W., DʼAstoli, P., Blakesley, R. E., Reasner, D. S., OʼDea, C. R., & Cash, B. D. (2020). Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study. Pain, 161(5), 1027-1036. https://doi.org/10.1097/j.pain.0000000000001754