TD-1211 - an inhibitor of the mµ-opioid receptor - alleviates chronic noncancer-related constipation in patients receiving opioid therapy, without affecting pain relief, show the results of a parallel-group study.
Patients who received any of the three doses of TD-1211 tested in the trial had significantly increased rates of complete spontaneous bowel movements (CSBMs) per week after 5 weeks compared with their counterparts who received placebo, report the researchers.
Furthermore, none of the participants in either group stopped using their central nervous system (CNS) opioids, nor was analgesic efficacy disturbed in any of the patients. The findings were presented at the American College of Gastroenterology 2012 Annual Scientific Meeting and Postgraduate Course.
"A majority of patients reported their constipation was better or much better on treatment, and response to treatment was clinically meaningful," said co-author Lynn Webster, from Lifetree Clinical Research in Salt Lake City, Utah, USA in a statement to the media.
A total of 217 patients with opioid-induced constipation were randomly assigned to either TD-1211 or to placebo. All patients assigned to the former received a 5 mg dose for the first 4 days, after which they were dose-escalated to either 10 mg or 15 mg for the remainder of the 5 weeks.
During weeks 2-5 of treatment, CSBMs increased by 0.8 per week among placebo-treated patients, a significantly smaller increase than was seen in patients who received 5, 10, and 15 mg, for whom CSBMs rose by 2.7, 3.4, and 3.7 per week, respectively.
Furthermore, significantly more patients who received TD-1211 at each dose achieved the prespecified response criteria of at least three SBMs per week plus an increase from baseline of at least one SBM per week for 3 or more weeks, at 59%, 61%, and 70% for 5, 10, and 15 mg, respectively, compared with 39% for placebo.
The most common adverse events reported by patients in the TD-1211 groups were abdominal pain, at 13%, versus 11% among placebo-treated patients, nausea, at a respective 9% versus 4%, diarrhea, at 9% versus 0%, and headache, at 5% versus 6%. The majority of these symptoms were associated with treatment initiation, remark Webster et al, and resolved within a few days.
Finally, "we observed no treatment-related serious adverse events and no evidence of CNS penetration, interference with analgesia, or central withdrawal," commented Webster.
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