Emend improves gastroparesis symptoms, fails to reach endpoint
LAS VEGAS — Oral Emend improved gastroparesis symptoms based on commonly used gastroparesis measures in a randomized controlled trial, according to the APRON results presented at ACG 2016.
However, the primary endpoint of improved nausea based on patient-reported visual analogue scale was not achieved.
Emend (aprepitant, Merck) is a neurokinin-1 receptor antagonist currently approved for the prevention of chemotherapy-induced nausea and vomiting in combination with other anti-emetics, and prevention of postoperative nausea and vomiting.
“Despite recent advances in pathophysiology we still do not have any disease modifying agents, and we neither have very good symptom-related agents when it comes to taking care of patients who might have gastroparesis nor patients who have symptoms that are suggestive of gastroparesis but have normal gastric activity,” Gianrico Farrugia, MD, from the Mayo Clinic, said during his presentation. “There’s therefore a significant burden of disease ... [and] we have this unmet need for better symptomatic treatment.”
Pankaj Jay Pasricha
To determine whether treatment with aprepitant results in symptomatic improvement in patients with either gastroparesis or gastroparesis-like symptoms, Farrugia and colleagues, including Pankaj Jay Pasricha, MD, MBBS, from Johns Hopkins University School of Medicine, randomly assigned 126 patients with nausea and vomiting and suspected gastric dysfunction to receive either 125 mg oral aprepitant daily or placebo for 4 weeks.
The primary endpoint was attaining at least a 25 mm reduction in the 4-week mean patient-reported visual analogue scale for nausea, or attaining a 4-week mean visual analogue scale score of less than 25 mm. Gastroparesis Cardinal Symptom Index (GCSI) and global Gastrointestinal Symptom Rating Scale (GSRS) scores were also evaluated.
Overall, 57% of patients had delayed gastric emptying and the remainder had gastroparesis symptoms with normal or rapid emptying. Twenty-nine percent of the patients had diabetes.
Comparable proportions of the treatment and placebo groups achieved the primary endpoint (46% vs. 40%; RR = 1.2; 95% CI, 0.8-1.7). However, the aprepitant group experienced significantly greater reductions in mean 4-week daily hours of nausea (–2.5 vs. –1.2 hours; P = .03), and mean 4-week GCSI scores (–1.3 vs. –0.7; P =.001). They also experienced greater symptom improvements based on multiple PAGI-SYM and GSRS measures, including overall symptom relief, nausea, vomiting, postprandial fullness, bloating and abdominal pain.
Adverse effects occurred in 31.7% of the treatment group compared with 15.9% of the placebo group, none of which were serious, and most of which were mild to moderate in severity and expected.
“In conclusion, as compared with placebo, 4 weeks of aprepitant did not meet our primary outcome ... However, using some of the common measures of nausea and gastroparesis symptoms, aprepitant did result in significant overall symptom relief, significant improvement in GCSI scores for nausea, vomiting postprandial fullness, bloating and abdominal pain,” Farrugia said. “Therefore, overall these data suggest that aprepitant has potential for effective and safe improvement of a variety of symptoms both in gastroparesis and related disorders.” – by Adam Leitenberger
Pasricha PJ, et al. Abstract #1. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 17-19, 2016; Las Vegas, NV.
Disclosures: This study was funded by a UO1 grant from NIDDK. Pasricha reports consulting for Vanda Pharma, which is developing a neurokinin-1 receptor antagonist.