Opioid-induced constipation: linaclotide shows benefit in phase 2 trial

  • Pain

  • curated by Kelli Whitlock Burton
  • Clinical Essentials
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • Linaclotide was significantly more effective at treating opioid-induced constipation (OIC) than placebo in patients whose chronic noncancer pain syndromes were managed with opioid therapy.

Why this matters

  • OIC is the most common adverse effect of chronic opioid use.

Study design

  • Multicenter, randomized, double-blind, placebo-controlled, phase 2 trial.
  • 254 patients with OIC with chronic noncancer pain syndromes managed with opioids received linaclotide 145 μg/day (n=87) or 290 μg/day (n=88) or placebo (n=79) for 8 weeks.
  • Funding: Allergan plc; Ironwood Pharmaceuticals, Inc.

Key results

  • Significantly greater increase in weekly spontaneous bowel movements with linaclotide vs placebo:
    • 1.6 with placebo.
    • 2.9 with 145 μg (P<.01 vs placebo>
    • 3.5 with 290 μg (P<.0001 vs placebo>
  • Significantly greater increase in the Bristol Stool Form Scale, indicating softer stools with linaclotide:
    • 0.9 with placebo.
    • 1.7 with 145 μg (P<.001 vs placebo>
    • 1.9 with 290 μg (P<.001 vs placebo>
  • OIC severity scores were significantly better with linaclotide:
    • −0.6 with placebo.
    • −1.0 for 145 μg (P=.0088 vs placebo).
    • −1.1 for 290 μg (P<.0001 vs placebo>
  • The most common treatment-related adverse event was diarrhea.
  • Serious adverse events were reported in 1 patient in the 290-μg group and 5 in the placebo group.

Limitations

  • Small treatment population, short-term follow-up.