1239 Clinical Safety of RHB-105: A Novel Rifabutin Based Triple Therapy for the Treatment of Helicobacter pylori Infection

Abstract

INTRODUCTION: Increasing H. pylori antimicrobial resistance has resulted in a need for new, improved therapies and recognition by the World Health Organization as a high priority for development of safe and effective treatment options. Rifabutin is an approved antibiotic whose most commonly reported adverse event (AE) is chromaturia. However, daily dosing of 300 mg rifabutin has historically demonstrated some safety concerns including neutropenia, leukopenia and thrombocytopenia. Our research suggests that a lower divided rifabutin dose is effective in H. pylori eradication without concerns of myelotoxicity. METHODS: This phase 3 data review is a safety assessment of RHB-105 (all-in-one fixed oral capsule formulation: rifabutin 50 mg, amoxicillin 1000 mg, omeprazole 40 mg) Q8H in treatment naive H. pylori infected patients. In two phase 3 studies, 573 US subjects were randomized to receive RHB-105 (n = 305), placebo (n = 41), or active comparator (n = 227) for 14 days. The first study compared RHB-105 with placebo (77:41 subjects) while the second study compared RHB-105 with active comparator (amoxicillin 1000 mg, omeprazole 40 mg, without rifabutin) 228:227 subjects. RESULTS: RHB-105 was well tolerated compared to either placebo or active comparator and the proportion of subjects reporting AEs were generally similar (41.0%, 46.3% vs 34.8%, respectively). AEs occurring in ≥1% of RHB-105 patients vs active comparator were diarrhea (9.5% vs 7.5%), chromaturia (3.0% vs 0.0%), abdominal pain (2.8% vs 1.8%) and vomiting (1.3% vs 0.9%). AEs occurring in ≥1% RHB-105 patients vs placebo were nausea (3.6% vs 2.4%), and chromaturia (3.0% vs 2.4%). Myelotoxicity was not reported in either study. Four SAEs (RHB-105: 2, Placebo: 1, Active comparator: 1) were reported but no deaths were reported. The two SAEs in RHB-105 patients included anemia and diabetic ketoacidosis with neither considered treatment related. Treatment discontinuation due to AE occurred in 4 patients (1.3%) receiving RHB-105, 1 (2.4%) placebo and 1 (0.4%) active comparator. AEs leading to discontinuation of RHB-105 were nausea (occurring in 2 patients), vomiting, and nasal congestion with cold-like symptoms occurring in 1 patient each, respectively. CONCLUSION: RHB-105, a low-dose rifabutin based regimen appears to be a generally well-tolerated treatment option for patients with H. pylori infection. As expected, chromaturia was reported more frequently in RHB-105. Importantly myelotoxicity was not reported.