S0457 Six-Month Efficacy of Polyethylene Glycol (PEG) 3350 in the Treatment of Chronic Idiopathic Constipation: Analysis Using FDA Endpoints

Abstract

INTRODUCTION: PEG 3350 is an osmotic laxative approved by the FDA for the treatment of constipation in 1999 and available OTC since 2006. Studies establishing the efficacy of PEG 3350 were performed prior to the establishment of standard constipation efficacy endpoints. This post-hoc analysis re-evaluates data from a previously published trial (DiPalma J, et al. Am J Gastroenterol 2007;102:1436-1441; NCT00153153) using the FDA weekly responder definition for chronic idiopathic constipation (CIC). The overall response was analyzed using multiple intervals across 6 months. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy of PEG 3350 vs placebo in patients with CIC (modified ROME criteria). Adults with CIC were randomized (2:1) to receive PEG 3350 17g or placebo once daily for 6 months (24 weeks). This new analysis assesses the FDA CIC endpoint, defined as a weekly CSBM response (i.e., ≥3 complete spontaneous bowel movements (CSBMs) per week and an increase of ≥1 CSBM from baseline) during at least 9 of 12 treatment weeks, including 3 of the last 4 weeks of this period. Similar criteria were used to assess weekly CSBM response for the full duration of the study using an 18/24-week endpoint. Additionally, less stringent weekly CSBM response rate was analyzed using 6/12- and 12/24-week endpoints. All analyses were also completed for weekly spontaneous bowel movement (SBM) response. RESULTS: The intention-to-treat population included 204 PEG 3350–treated and 100 placebo-treated patients. At baseline, mean CSBMs (<1/wk) and mean SBMs (≤4/wk) rates were similar in both treatment arms. Weekly CSBM response for 9/12 weeks (FDA CIC endpoint) was significantly higher in the PEG 3350 group vs placebo (42% vs 13%; P < 0.0001) (Table 1). Response remained consistent for the 18/24-week CSBM analysis (43% vs 11%; P < 0.0001). Similar results were seen across the 9/12-week and 18/24-week SBM endpoints. Response rates for the 6/12-week and 12/24-week endpoints were higher for both CSBM and SBM showing overall consistency in the clinical benefits of PEG 3350 for CIC patients (P < 0.0001; Figure 1). CONCLUSION Using current definitions of treatment response based on the FDA CIC CSBM endpoint and improvements in SBM, once-daily PEG 3350 demonstrated substantial and sustained efficacy in patients with CIC over a period of 6 months.Figure 1.: CSBM and SBM response rates using different time intervalsTable 1.: CSBM and SBM outcomes