Entereg (alvimopan) capsules accelerated gastrointestinal (GI) recovery in patients undergoing laparotomy for bowel resection or radical hysterectomy, according to the phase 3 clinical study (14CL313) published in the October issue of the Annals of Surgery, In addition, the data in the publication indicated that in this study hospital discharge orders were written for patients taking 12 mg of Entereg about one day earlier as compared with those taking placebo.
Entereg is an investigational peripherally-acting mu opioid receptor antagonist designed to block the negative effects of opioids, like morphine, on the gastrointestinal system without interfering with the analgesic effects on the central nervous system. It is the first of this new class with a New Drug Application (NDA) that has been accepted for review by the Food and Drug Administration (FDA). The NDA for Entereg includes the results of Study 313 and two other efficacy studies.
Entereg was evaluated in this clinical trial for the management of postoperative ileus (POI). POI is a transient impairment of GI motility and function, which can occur frequently in patients undergoing abdominal surgery. Adolor Corporation and GlaxoSmithKline are collaborating on the worldwide development and commercialization of Entereg.
"There are no drugs approved by the FDA for the management of POI," notes the study's lead author Bruce G Wolff, professor of Surgery, Mayo Medical School, and Consultant in Colon & Rectal Surgery, Mayo Clinic in Rochester, Minnesota. "The potential benefits from managing POI may include the reduction in the incidence of bowel complications, the potential for more rapid return to normal bowel function, improved patient comfort and reduced length of hospital stay."
Dr. Wolff continued, "The results from this study are promising by reporting that Entereg accelerated recovery of gastrointestinal function and time to hospital discharge order written as compared with placebo in patients with POI after undergoing bowel resection or radical total abdominal hysterectomy surgery."
Several factors are thought to contribute to the onset of POI. These include the physical stress of surgery, inhaled anaesthesia, use of pain-relieving opioids during and after surgery, endogenous opioids, and changes in electrolyte and fluid balance. POI can contribute significantly to discomfort during recovery, lengthen the time spent in the hospital, and can increase the risk of hospital readmission. Symptoms of POI include nausea, vomiting, inability to tolerate solid food, gas and fluid accumulation in the bowel, delayed passage of gas or stool, and pain.
This randomized, double-blind, placebo-controlled multi-centre study included 510 patients scheduled for bowel resection or radical total abdominal hysterectomy. Patients received either Entereg 6 mg, Entereg 12 mg, or placebo orally two or more hours before surgery, then twice daily until hospital discharge or for up to 7 days.
Importantly, the study reports that treatment with Entereg did not interfere with opioid analgesia as measured by average daily postoperative opioid consumption and daily and maximum postoperative pain scores. The study also reports that Entereg also appeared to decrease hospital readmission rates.
Many patients undergoing abdominal surgery experience transient gastrointestinal impairment. This condition, known as postoperative ileus, may be exacerbated and prolonged by multiple factors including the use of opioid analgesics for pain relief. POI is characterized by abdominal distension and pain, nausea and vomiting, reduced desire to eat, and an inability to pass gas or stool. POI is a major contributor to prolonged hospital stays. Consequently, POI represents a substantial burden on healthcare resources.
Despite the negative impact, there have been few advances in the treatment of POI since the introduction of nasogastric decompression over 100 years ago, which has limited effectiveness and is uncomfortable for patients. Currently, there are no drugs approved for the management of POI.
Adolor Corporation and GlaxoSmithKline are collaborating on the worldwide development and commercialization of Entereg for POI, opioid-induced bowel dysfunction (OBD) associated with extended use of opioids to treat chronic pain, chronic constipation not associated with opioid use, and irritable bowel syndrome (constipation predominant).