A new formulation of tolevamer, a novel nonantibiotic polymer, is safe and well‐tolerated in healthy volunteers: a randomized phase I trial

Abstract

To evaluate the safety and tolerability of a new oral solution formulation of tolevamer potassium sodium, a nonantibiotic polymer that binds Clostridium difficile toxins A and B. This phase 1 randomized, double-blind, placebo-controlled study evaluated four doses of tolevamer potassium sodium in 40 healthy volunteers using a sequential dose escalation paradigm and doses of 6, 9, 12 and 15 g day(-1) for 9 days. Within each 10 patient cohort, eight patients received active treatment and two matching placebo. Placebo subjects were pooled to provide eight per arm. All subjects received three times daily dosing on days 2-8 as well as a loading dose (a single dose equal to the total daily dose) either on day 1 or day 9. All 40 subjects completed the study per protocol. Treatment-emergent adverse events (TEAEs) were generally mild, transient, and resolved without sequelae. There were no serious AEs or deaths. There was no relationship detected between dose and the incidence of TEAEs, whether drug-related (all gastrointestinal disorders) or not. No clinically significant changes in laboratory parameters, including serum and urinary potassium concentrations, vital signs, and results of physical examination, were observed. A small but statistically significant reduction in 24 h urine potassium excretion was seen in the 15 g day(-1) dose group, and on day 10 in the 6 g day(-1) group. Tolevamer oral solution administered for 9 days at total daily doses up to 15 g, with loading doses of up to 15 g, was generally safe and well-tolerated in healthy volunteers.