Novel Rabeprazole Extended-Release 50 mg vs. Esomeprazole 40 mg in Healing of L.A. Grade C/D Erosive GERD: Results of Two Double-Blind Randomized Trials

Abstract

Purpose: Currently available PPIs may not achieve desired outcomes in patients with GERD due to a limited duration of acid inhibition over a 24-hr period. A novel rabeprazole extended-release formulation (RAB-ER) was designed to provide longer duration of drug exposure and gastric acid suppression without increased peak concentration with the intent to improve outcomes such as healing, especially in patients with more severe esophagitis. Methods: Symptomatic patients with Los Angeles (L.A.) Grade C or D esophagitis were randomly assigned to RAB-ER 50 mg or esomeprazole (ESO) 40 mg qAM in 2 identical randomized double-blind trials. Upper endoscopy was performed at 4 wks and again at 8 weeks if esophagitis was unhealed at 4 wks. Two primary endpoints were tested sequentially in the “ITT” population (all randomized patients receiving ≥1 dose of study drug): 1) healing by 8 weeks (hypothesis: RAB-ER non-inferior to ESO (8% non-inferiority margin)) and 2) healing at 4 weeks (hypothesis: RAB-ER superior to ESO (p<0.05)). The secondary endpoint was diary-recorded sustained heartburn resolution (≥7 consecutive heartburn-free days) at week 4. Subgroup analyses for Grade C and Grade D esophagitis also were pre-specified. Results: Results for the primary and secondary endpoints in the overall ITT study population are shown in Table 1. Subgroup analyses for Grade C esophagitis and for Grade D esophagitis are shown in Table 2.[3] Table 1. Results of primary and secondary endpoints in L.A. grade C/D erosive esophagitis[3] Table 2. Results of subgroup analyses for L.A. Grade C and L.A. Grade D erosive esophagitisConclusion: In patients with Grade C/D esophagitis, RAB-ER was as effective as ESO. Although the results of our primary endpoint do not support our hypothesis that longer acid inhibition would significantly improve early healing in C/D patients, subgroup analysis still suggests the possibility of a benefit in patients with more severe (Grade D) esophagitis but this hypothesis requires further evaluation. Disclosure: Laine: Consultant: Eisai, AstraZeneca, Novartis, Santarus; Research support; Takeda Katz: Consultant: Novartis, Takeda, Xenoport, Eisai; Lecture honoraria: Takeda Johnson: Consultant: AstraZeneca,Takeda, Esai, Novartis, Xenoport, Proctor and Gamble Research support: AstraZeneca, Takeda Ibegbu: Goldstein: Lu, Rossiter, Chou: Employees of Eisai. This research was supported by an industry grant from Eisai.