Randomised clinical trial: the long‐term safety and tolerability of naloxegol in patients with pain and opioid‐induced constipation. Issue 7 (12th August 2014)

• Record Type: Journal Article
• Authors: Webster, L.; Chey, W. D.; Tack, J.; Lappalainen, J.; Diva, U.; Sostek, M.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 40:Issue 7(2014)
• Page Start: 771
• Page End: 779
• Publication Date: 2014-08-12
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12899
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12899-abs-0001"> <title>Summary</title> <sec id="apt12899-sec-0001" sec-type="section"> <title>Background</title> <p>Opioid‐induced constipation (OIC) is a common adverse effect of opioid therapy.</p> </sec> <sec id="apt12899-sec-0002" sec-type="section"> <title>Aim</title> <p>To evaluate the long‐term safety and tolerability of naloxegol, an oral, peripherally acting μ‐opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC.</p> </sec> <sec id="apt12899-sec-0003" sec-type="section"> <title>Methods</title> <p>A 52‐week, multicenter, open‐label, randomised, parallel‐group phase 3 study was conducted in out‐patients taking 30–1000 morphine‐equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual‐care (UC; investigator‐chosen laxative regimen) treatment for OIC.</p> </sec> <sec id="apt12899-sec-0004" sec-type="section"> <title>Results</title> <p>The safety set comprised 804 patients (naloxegol, <italic>n</italic> = 534; UC, <italic>n</italic> = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment‐emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol‐emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations.</p> </sec> <sec id="apt12899-sec-0005" sec-type="section"> <title>Conclusion</title> <p>In patients with noncancer pain and opioid‐induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.</p> </sec> </abstract>