Clinical Trials Resource Center

New Medical Therapies™

Ileus

October 6, 2008

Tranzyme issued positive results from a phase IIb trial of TZP-101 for the treatment of post-operative ileus. This multinational, double-blind, placebo-controlled study enrolled 200 subjects undergoing open bowel resection surgery. The subjects received either TZP-101 or placebo administered intravenously within the first hour after surgery, followed by once-daily dosing for up to seven days. The primary endpoint was time to first bowel movement. TZP-101 was superior to placebo at all doses tested. For the two most effective doses, 80g/kg and 480g/kg , the median times to first bowel movement were 70.5 and 68.0 hours, respectively, versus 89.6 hours for placebo (p=0.056 and p=0.029, respectively). In addition, 64% of subjects in both the 80g/kg and 480g/kg dose groups had a bowel movement within 72 hours, versus only 25% in placebo; (p=0.001 for both dose groups). The secondary endpoint, the percentage of subjects achieving gastrointestinal recovery within 72 hours of surgery, also reached statistical significance. The median times for this endpoint were 70.5 and 68.0 hours for the 80g/kg and 480g/kg groups, respectively, versus 91.3 hours for placebo (p=0.034 and p=0.044, respectively). TZP-101 was well tolerated. Based on the results Tranzyme plans to commence phase III trials early in 2009.

May 15, 2006

Tranzyme reported positive results of a phase I trial of TZP-101, for the treatment of gastrointestinal motility disorders including post-operative ileus. This placebo-controlled single-ascending dose study enrolled 48 healthy volunteers, who received 1 of 6 doses of the drug or placebo via 30 minute intravenous infusion. Trial data indicated that treatment was safe and generally well tolerated, with no serious adverse events reported. Pharmacokinetic data were supportive of further clinical development. Based on these results, the company announced plans to initiate both a multiple-dose safety and pharmacokinetic study of the drug in healthy volunteers and a single-dose study in Type-1 diabetes patients suffering from poor GI motility in the near future.

February 13, 2006

Adolor and GlaxoSmithKline have reported positive results of a phase III trial, dubbed Study 14CL314, of Entereg (alvimopan) for the treatment of post-operative ileus. Trial data met their primary efficacy endpoint, yielding a significantly shorter (˜20 hours sooner) time to recovery of gastrointestinal function, a composite endpoint which included time to tolerability of solid foods and time to first bowel movement, compared to placebo (hazard ratio=1.53; p<0.001). Secondary endpoints were also met, including time to secondary composite GI function (including times to first bowel movement, ready for discharge, discharge order written and hospital departure; ~16 hours sooner; HR=1.45, p<0.001), and time to discharge order written (˜18 hours sooner; HR=1.40, p<0.001). Treatment was generally well tolerated. This randomized, placebo-controlled study enrolled 654 patients scheduled for surgical bowel resection, who were to receive 12 mg of the drug or placebo twice daily, starting 30-90 minutes prior to surgery.

January 3, 2005

Adolor Corporation reported initial results from a phase III trial investigating alvimopan (Entereg), a peripherally-restricted mu opioid receptor antagonist for the treatment of postoperative ileus. The multi-center, randomized, double-blind, placebo controlled parallel group study, designated SB-767905/001, enrolled 911 subjects who had undergone bowel resection or radical hysterectomies. The primary endpoint of the study is the time to recovery of GI function, as defined by the later of the following two events: time from surgery until the patient first tolerates solid foods and time from surgery until the patient first passes flatus or has a bowel movement. Results showed a hazard ratio of 1.22 and 1.13 for the 6mg and 12mg respectively, each as compared to the placebo group, a non-statistically significant result. Secondary endpoints included an additional measure of time to recovery of gastrointestinal function (GI2), which measures GI recovery based on tolerating solid food and bowel movement. These results were statistically significant as compared to the placebo group. Alvimopan was generally well tolerated in this study. The study was conducted in Europe, Australia and New Zealand and was performed to support a Marketing Authorization Application (MAA) in the European Union. GSK and Adolor are collaborating on the worldwide development and commercialization of alvimopan.

September 27, 2004

Adolor and GlaxoSmithKline reported positive results of their phase III trial of Entereg, their peripheral mu-opioid-receptor antagonist, for the treatment of post-operative ileus (POI) and gastrointestinal recovery in subjects undergoing bowel resection or radical hysterectomy. Trial data met their primary endpoints, significantly reducing time to GI function rebound and hospital discharge at the higher dosing regimen. Furthermore, the drug did not interfere with opioid analgesia. The double-blind, placebo-controlled multi-center study randomized 510 subjects scheduled for bowel resection or complete radical hysterectomy to receive one of two doses of Entereg (6 mg or 12 mg) or placebo prior to surgery, then twice daily until hospital discharge (up to 7 days). The drug was found to be safe and well tolerated at both treatment doses. These data are part of Entereg’s NDA, currently under review by the FDA. If approved, the drug would become the only marketed therapy for post-operative ileus.

January 19, 2004

Adolor reported positive results from a phase III trial investigating Entereg (alvimopan), an opioid narcotic antagonist for the treatment of postoperative ileus (POI). Results showed a positive trend with regards to the time to recovery of gastrointestinal function, when Entereg (6 mg and 12 mg groups) was compared to placebo. Data demonstrated a statistically significant differences in time to hospital discharge order written in each of the 6 mg and 12 mg treatment groups (14 and 15 hours sooner) as compared to placebo group. The study (called 14CL308) enrolled 666 subjects who were scheduled to undergo large or small bowel resections, or simple or radical hysterectomy. The treatments were generally well tolerated with the most frequently adverse events being nausea, vomiting, and pruritus.

October 27, 2003

Adolor reported positive results from a phase III trial investigating Entereg (alvimopan), an opioid narcotic antagonist for the treatment of postoperative ileus. Entereg was generally well tolerated with over 90% of subjects completing treatment in both groups. The most frequently observed adverse events in both groups were nausea, vomiting and constipation. Discontinuations due to adverse events were 4% in the treatment group and 5% in the placebo group. The double-blind, randomized, placebo-controlled, multi-center study enrolled 519 subjects who received either Entereg (12 mg) or placebo, at least two hours prior to surgeries, and then twice a day on the first postoperative day. The study was designed to evaluate the safety of Entereg in subjects undergoing total abdominal simple hysterectomies. The company plans to report additional results at a later date.

October 6, 2003

Adolor reported positive results from a phase III trial investigating Entereg (alvimopan), an opioid narcotic antagonist for the treatment of postoperative ileus. Results showed a statistically significant difference in the primary endpoint, time to recovery of gastrointestinal function, with Entereg (6 mg - 12 mg) compared with placebo. The mean times of recovery were 120 hours, 105 hours, and 98 hours for the placebo, 6 mg, and 12 mg groups, respectively. Data showed a statistically significant difference in the 12 mg treatment group, in time to hospital discharge order written, compared with placebo. The multi-center, double-blind, placebo controlled study enrolled 510 subjects and was designed to for patients set to undergo major abdominal surgery and who were taking opioids for pain relief. Subjects were scheduled to undergo small bowel resections, large bowel resections or radical hysterectomies.

April 7, 2003

Aldor reported some positive results from a phase III trial investigating alvimopan for the treatment of postoperative ileus. Results showed that alvimopan (6 mg) subjects achieved a statistically significant difference in time to recovery of gastrointestinal function compared to the placebo group. Subjects in the 12-mg group achieved a positive trend toward recovery time; however, the difference from placebo was not statistically significant. Alvimopan was generally well tolerated in this study with the most frequently observed adverse events in both groups being nausea, vomiting and hypotension. The double blind, placebo-controlled, multi-centered study, called 14CL302, enrolled 450 subjects who were scheduled to undergo colectomies, hysterectomies and to receive opioid analgesics.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.