Looks like this latest Adolor trial was underpowered given the multiple arms. Note that in an earlier trial they got stat significance at the lower dose but not the higher. But still may be enough overall for approval, although I haven't followed them closely enough to have any confidence in this view:
Press Release Source: Adolor Corporation
Adolor Corporation Announces Top-Line Results in Entereg(TM) Phase 3 Clinical Study 308 in Postoperative Ileus
Tuesday January 13, 4:05 pm ET
- NDA Submission Targeted Late First Half 2004 - - Conference call and webcast at 5:45 p.m. ET on January 13, 2004 -
EXTON, Pa., Jan. 13 /PRNewswire-FirstCall/ -- Adolor Corporation (Nasdaq: ADLR - News) announced today top-line results of its Phase 3 clinical study (14CL308) of Entereg(TM) (alvimopan) in the management of postoperative ileus (POI). Study 14CL308 enrolled 666 subjects who were scheduled to undergo large or small bowel resections, or simple or radical hysterectomy.
In the primary endpoint of Study 14CL308, time to recovery of gastrointestinal function, a positive trend was observed when each of the Entereg(TM) 6 mg and 12 mg treatment groups was compared to the placebo group (Cox proportional hazard model: for 6 mg group, hazard ratio = 1.20, P = 0.079; for 12 mg group, hazard ratio = 1.24, P = 0.038).
A difference in favor of Entereg(TM) was observed for all of the secondary endpoints in both the 6 mg and 12 mg treatment groups. Statistically significant differences were achieved in time to hospital discharge order written in each of the 6 mg and 12 mg treatment groups as compared to the placebo group.
"We are pleased today to report results from Study 308," stated Bruce A. Peacock, president and chief executive officer of Adolor. "Our four Phase 3 clinical trials enrolled more than 2,000 subjects, which we believe represents a very substantial clinical development program. The completion of Study 308 supports our goal of submission of a New Drug Application for Entereg(TM) late in the first half of 2004."
Mean times to recovery of gastrointestinal function were approximately 8 hours and 10 hours sooner for each of the Entereg(TM) 6 mg and 12 mg treatment groups, respectively, as compared with the placebo group. Mean times to hospital discharge order written were approximately 14 and 15 hours sooner for each of the 6 mg and 12 mg treatment groups, respectively, as compared with the placebo group. For the approximately 437 subject subgroup of bowel resection subjects, mean times to hospital discharge order written were approximately 17 hours and 21 hours sooner for the 6 mg and 12 mg treatment groups, respectively, each as compared to the placebo group.
Entereg(TM) was generally well tolerated in this study. The most frequently observed adverse events in both the 6 mg and 12 mg treatment groups and the placebo groups were nausea, vomiting, and pruritus.
About Study 308 and the Entereg(TM) Postoperative Ileus Clinical
Development Program
Because each of the Entereg(TM) Phase 3 studies assessing efficacy involves multiple comparisons (i.e., two doses of Entereg(TM) versus placebo), under statistical techniques, statisticians control the overall study error rate (i.e., the likelihood that the drug response occurred by chance) by requiring that each of the multiple dose comparisons meet a P-value of P <0.05 to show statistical significance. Therefore, because the P-value for the 6 mg dose group was 0.079, the P-value of 0.038 achieved in the 12 mg group in Study 14CL308, while less than 0.05, is not considered statistically significant.
The clinical development program for the study of Entereg(TM) in postoperative ileus includes four Phase 3 clinical studies. Studies 14CL308, 14CL302 and 14CL313 were double-blind, placebo controlled, multi-center studies each designed to enroll subjects scheduled to undergo certain types of major abdominal surgery and receiving opioids for pain relief. Under these protocols, subjects were randomized into three arms to receive placebo, 6 mg, or 12 mg doses of Entereg(TM) at least two hours prior to surgery, and then twice a day beginning on the first postoperative day until hospital discharge or for a maximum of seven days. The primary endpoint in these three studies was a composite measure of the time to recovery of both upper and lower gastrointestinal function, whichever occurred last, as defined by time to tolerability of solid foods and time to either first flatus or first bowel movement, respectively.
Top-line results from Study 14CL302 were announced in April 2003. Study 14CL302 enrolled 451 subjects who were scheduled to undergo large bowel resections or simple or radical hysterectomies. A statistically significant difference was achieved in the primary endpoint of Study 14CL302, time to recovery of gastrointestinal function, in the Entereg(TM) 6 mg treatment group compared to the placebo group. A positive trend was observed in the primary endpoint of the study for the Entereg(TM) 12 mg treatment group; however, the difference from placebo was not statistically significant. The most frequently observed adverse events in both the placebo and treatment groups were nausea, vomiting and abdominal distension.
Top-line results from Study 14CL313 were announced in September 2003. Study 14CL313 enrolled 510 subjects who were scheduled to undergo small bowel resections, large bowel resections or radical hysterectomies. A statistically significant difference was achieved in the primary endpoint, time to recovery of gastrointestinal function in both the Entereg(TM) 6mg and 12 mg treatment groups when each was compared to placebo. The most frequently observed adverse events in both the placebo and treatment groups were nausea, vomiting and hypotension.
Top-line results from Study 14CL306 were announced in October 2003. Study 14CL306 was designed to assess safety as its primary objective and to assess efficacy as a secondary objective. Study 14CL306 enrolled 519 subjects who were scheduled to undergo simple hysterectomy and receive opioids for pain relief. Under this protocol, subjects were randomized to receive either Entereg(TM) 12 mg (approximately 400 subjects) or placebo (approximately 100 subjects), at least two hours prior to surgery, and then twice a day beginning on the first postoperative day for seven days on an inpatient or outpatient basis. Study 14CL306 was the first study where dosing continued on an out- patient basis after subjects were discharged from the hospital. Entereg(TM) was generally well tolerated in this observational safety study with 93% of subjects completing treatment in the Entereg(TM) 12 mg group and 92% of subjects completing treatment in the placebo group. The most frequently observed adverse events in both the placebo and treatment groups were nausea, vomiting and constipation.
Conference Call and Webcast Information
Adolor will be hosting a conference call and webcast on January 13, 2004 at 5:45 p.m. Eastern Time 2:45 p.m. Pacific Time to discuss these results. To participate in the audio portion and have the opportunity to pose questions, dial 1-800-299-7635 for domestic callers, and 1-617-786-2901 for international callers, and provide the Passcode 74813730 . Slides accompanying the call, as well as a webcast of the audio portion of the call, will be available on the Investor Relations section of the Company's website, www.adolor.com.
A replay of the conference call will be available beginning at 7:45 Eastern Time on January 13, 2004. To listen to a replay of the conference call, dial 1-888-286-8010 (domestic callers) or 1-617-801-6888 (international callers) with a Passcode of 65558109 or listen via the website. The replay will be available for one week.
JPMorgan Healthcare Conference
Adolor is participating in the 22nd Annual JPMorgan Healthcare Conference in San Francisco, California. The company's presentation is scheduled for 1:30 p.m. Pacific Time 4:30 p.m. Eastern Time on Tuesday, January 13, 2004. Bruce A. Peacock, president and chief executive officer, will present an overview of the company. A live and on-demand webcast of the presentation will be accessible on the Company's website, www.adolor.com, in the Investor Relations section during the presentation, and archived audio of the presentation, including PowerPoint slides, will be available through January 20, 2004. |
