Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. — VialBase Research

Summary

This multicenter, double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov NCT00672074) evaluated intravenous ipamorelin, a ghrelin-receptor agonist, for the management of postoperative ileus in adults undergoing small or large bowel resection by open or laparoscopic surgery. Patients received 0.03 mg/kg ipamorelin or placebo twice daily from postoperative day 1 through day 7 or hospital discharge. Of 117 patients enrolled, 114 comprised the safety and modified intent-to-treat populations, with demographic and disease characteristics balanced between arms. The key efficacy endpoint — time from first dose to tolerance of a standardized solid meal — was numerically shorter with ipamorelin (25.3 h) than placebo (32.6 h), but this difference did not reach statistical significance (p = 0.15). Treatment-emergent adverse events were reported in 87.5% of the ipamorelin group versus 94.8% of the placebo group. The authors concluded that ipamorelin was well tolerated at this dose and schedule, but no significant differences from placebo were observed in the key or secondary efficacy analyses.

Key Findings

• Randomized, double-blind, multicenter, placebo-controlled design testing IV ipamorelin 0.03 mg/kg BID versus placebo for up to 7 postoperative days in bowel resection patients (NCT00672074)
• 117 patients enrolled (114 in the safety/modified intent-to-treat populations), with balanced demographic and disease characteristics between groups
• Primary endpoint — time to tolerance of a standardized solid meal — favored ipamorelin numerically (25.3 h vs. 32.6 h) but the difference was not statistically significant (p = 0.15)
• Ipamorelin was well tolerated: treatment-emergent adverse event incidence was actually lower than placebo (87.5% vs. 94.8%)
• No statistically significant differences between ipamorelin and placebo were found in the key or secondary efficacy analyses, and the authors noted the study’s small, heterogeneous proof-of-concept design as a limitation

Relevance to Ipamorelin

This proof-of-concept trial preceded the later phase 3 postoperative ileus program and offers an earlier, more cautious data point on ipamorelin’s prokinetic potential in a surgical GI-motility context. While the safety profile was favorable and the direction of the meal-tolerance effect trended toward benefit, the trial did not meet statistical significance on its primary efficacy endpoint, so it should not be cited as clinical proof of GI-motility efficacy on its own. It is best read alongside later ipamorelin postoperative ileus data as part of the broader evidentiary picture rather than as a standalone confirmation of effect.

Citation

Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. International Journal of Colorectal Disease. 2014;29(12):1527-34. doi:10.1007/s00384-014-2030-8.

See Also

• Parent compound: Ipamorelin