PURPOSE: Ghrelin agonist TZP-101 is a potent prokinetic. This phase 2b study evaluated TZP-101 safety and efficacy in postoperative ileus management.
METHODS: Adults undergoing open partial colectomy were adaptively randomized to receive 20, 40, 80, 160, 320, 480 or 600 μg/kg TZP-101 (n = 168) or the placebo (n = 68) by 30-minute IV infusion within 1 hour of surgical closure and then daily for up to 7 days. The primary efficacy end point was the time to first bowel movement. Secondary end points included the percentage of patients with return of gastrointestinal function within 72 hours, and the time to readiness for discharge.
RESULTS: TZP-101 accelerated the time to first bowel movement in all groups, with Cox proportional hazard ratios of 1.57 (P = .056) for the low-efficacious dose (80 μg/kg) and 1.67 (P = .03) for the most efficacious dose (480μg/kg). Using Kaplan-Meier analysis, the median time to first bowel movement was reduced in all TZP-101 groups by 10 to 22 hours vs. the placebo. A greater number of patients who received TZP-101 achieved recovery (P ≤ .001) by 72 hours postsurgery compared with the placebo. The median time to readiness for hospital discharge was significantly accelerated by 20.4 hours at the 480 μg/kg TZP-101 dose compared with the placebo (hazard ratio = 1.69; P = .03). The most common treatment-emergent adverse events were nausea and vomiting, which were reduced in the TZP-101 group compared with the placebo group.
CONCLUSION: In patients undergoing major abdominal surgery, the first-in-class ghrelin agonist TZP-101 was well-tolerated and accelerated recovery of the upper and lower gastrointestinal tract, with a large proportion of subjects recovering within 72 hours compared with the placebo.
1 Institutul Clinic Fundeni, Bucharest, Romania
2 Cedars-Sinai, Los Angeles, California
3 Georgetown University, Washington, District of Columbia
4 Tranzyme Pharma Inc., Research Triangle Park, North Carolina
5 Spectrum Health, Grand Rapids, Michigan
This work was supported by Tranzyme Pharma Inc.
Financial Disclosure: Gordana Kosutic and Philippa A. Charlton are employees of Tranzyme Pharma, Inc., the study sponsor. John Pezzullo is a Tranzyme Pharma consultant performing statistical analysis for the study. Anthony J. Senagore was a study investigator and also an advisor to Tranzyme Pharma. Irinel Popescu and Phillip R. Fleshner were study investigators who have no other disclosures with respect to the study sponsor.
Presented at the meeting of The American Society of Colon and Rectal Surgeons, Hollywood, FL, May 2 to 6, 2009.
Correspondence: Anthony J. Senagore, M.D., M.B.A., M.S., Michigan State University/CHM, 25 Michigan St NE, Suite 4300 MC038, Grand Rapids, MI 49503.