Polyethylene glycol 3350 plus electrolytes for chronic constipation: a 2-week, randomized, double-blind, placebo-controlled study with a 52-week open-label extension

Atsushi Nakajima,Kazuhiko Shinbo,Yoshikazu Kinoshita,Akira Oota

doi:10.1007/s00535-019-01581-x

Abstract

BackgroundAlthough polyethylene glycol 3350 plus electrolytes (PEG3350 + E) is the most widely used osmotic laxative in Europe, prospective data on its long-term (over 6 months) safety and efficacy are not available to date.MethodsJapanese patients with chronic constipation were randomized to receive PEG3350 + E or placebo for 2 weeks orally. Following this, the patients received PEG3350 + E in the 52-week extension study. The starting dose was 13.7 g/day dissolved in 125 mL of water, and dose titration was allowed (upper limit 41.1 g/day) according to the patient’s bowel condition. The primary efficacy endpoint was the change from baseline in frequency of spontaneous bowel movements (SBMs) at week 2 in the double-blind study. Secondary endpoints and adverse events were assessed. Safety and efficacy were also assessed in the extension study.ResultsAmong 204 patients who provided informed consent, 156 were randomized and included in the full analysis. The frequency of SBMs was significantly higher with PEG3350 + E [least squares mean (LSM) 4.3, 95% confidence interval (CI) 3.6–4.9] compared with placebo (LSM 1.6, 95% CI 1.2–2.1; P < 0.0001). A total of 153 patients entered the extension study; PEG3350 + E led to a sustained improvement in bowel function. The common adverse drug reactions during the entire study period were mild gastrointestinal disorders (abdominal pain 4.5%, diarrhea 3.8%, nausea 3.2%, abdominal distension 2.6%).ConclusionsTreatment with PEG3350 + E resolved constipation in the short term, was well tolerated, and led to sustained improvement in bowel function in the long-term treatment of Japanese patients with chronic constipation.Clinical trial registration numberJapic CTI-163167.

Highlights

Chronic constipation (CC) is one of the most common chronic gastrointestinal symptoms
The frequency of spontaneous bowel movements (SBMs) was significantly higher with PEG3350 ? E [least squares mean (LSM) 4.3, 95% confidence interval (CI) 3.6–4.9] compared with placebo (LSM 1.6, 95% CI 1.2–2.1; P \ 0.0001)
A significantly higher increase in the primary endpoint of change in the frequency of SBMs from baseline at week 2 was observed in the PEG3350 ? E group [LSM (SE) 4.3 (0.2), 95% CI 3.6–4.9] than in the placebo group [LSM (SE) 1.6 (0.3), 95% CI 1.2–2.1; P \ 0.0001; Table 2]

Summary

Introduction

Chronic constipation (CC) is one of the most common chronic gastrointestinal symptoms. Patients with CC suffer from infrequent bowel movements, straining, sensation of incomplete evacuation, and hard stools. CC is most often defined by the Rome IV diagnostic criteria for functional constipation published in 2016 [1] (these criteria were unchanged from the 2006 version [2]). About 28.4% of Japanese adults have self-reported constipation [7]. Current management for CC usually begins with lifestyle modifications, in which the physician increases the patient’s dietary fiber as well as fluid intake and amount of exercise. 3350 plus electrolytes (PEG3350 ? E) is the most widely used osmotic laxative in Europe, prospective data on its longterm (over 6 months) safety and efficacy are not available to date

Methods

Results

Conclusion