ORLANDO, Fla. -- University of Michigan gastroenterologist William Chey, M.D., presented promising data at the Digestive Diseases Week meeting about an investigational drug to relieve opioid-induced constipation.
Globally, approximately 28 million to 35 million, or nearly half, of patients taking opioids for long-term pain develop constipation. About 40 percent to 50 percent of sufferers will find relief from over-the-counter or prescription laxatives.
Two phase 3 studies sponsored by AstraZeneca showed a 25 mg dose of the investigational drug naloxegol safely increased bowel movements among opioid-induced constipation sufferers, compared to a placebo, and the effects were maintained over a 12-week treatment period.
Naloxegol is a peripherally-acting mu-opioid receptor antagonist, which has been specifically designed for the treatment of constipation, a common and often debilitating side effect of prescription opioid pain medicines used for osteoarthritis, cancer, and chronic back pain.
“For the more than 69 million chronic pain opioid users world-wide, opioid-induced constipation is the most common side effect,” says Chey, AGAF, FACG, FACP, professor of internal medicine at the U-M Health System. “These data suggest that naloxegol may be an important treatment option for patients struggling with opioid-induced constipation.”
The Phase III studies known as KODIAC, enrolled 652 people in one trial and 700 in another. The 12-week, multicenter, randomized, double blind, placebo-controlled pivotal trials evaluated 12.5 mg and 25 mg doses of naloxegol, once-daily.
The primary endpoint, or desired goal, in both trials was percentage of opioid-induced constipation (OIC) responders, versus placebo, over 12 weeks of treatment. The secondary endpoints included the 12-week response rate in a laxative inadequate response population, the median time to first spontaneous bowel movement (SBM) and the number of days per-week with at least one bowel movement.
Data presented showed that naloxegol resulted in significantly more OIC responders and increased the frequency of SBMs, for the 25 mg dose. The 12.5 mg dose did not show statistical significance.
Specific data from these studies showed:
- In key secondary endpoints, the 25 mg dose demonstrated a statistically significant effect compared to placebo in patients with laxative inadequate response (LIR), time to first SBM post first dose, and days per week with at least one SBM.
- The median time to first post-dose SBM was 6-12 hours on 25 mg compared to 36-38 hours on placebo.
- The most common treatment-emergent side effects were abdominal pain, diarrhea and nausea which occurred more frequently in patients receiving naloxegol 25 mg/d than in the other groups.
- There were four major adverse cardiovascular events (PBO 2; 25mg 1; 12.5 mg 1) across all major arms of the study as adjudicated by an independent third party panel of reviewers.
- There was no reported reversal or reduction of opioid-mediated analgesia as reflected by daily pain scores and opioid dose.
Plans for naloxegol will be finalized over the coming months, incorporating the outcome of ongoing discussions with health authorities in the U.S., European Union and Canada.
Disclosure: Chey serves as a paid consultant to AstraZeneca
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