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

Abstract

Background: Although 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.

Methods: Japanese 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.

Results: Among 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%).

Conclusions: Treatment 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 number: Japic CTI-163167.

Keywords: Chronic constipation; Polyethylene glycol 3350 plus electrolytes; Prospective long-term clinical trial; Spontaneous bowel movement.

Fig. 1

Patient disposition. PEG3350 + E polyethylene glycol 3350 plus electrolytes. *n = 2; one subject each experienced vertigo positional and contusion. **n = 8; one subject each experienced infectious colitis, breast cancer, insomnia, abdominal discomfort, constipation, nausea, eczema, and erythema

Fig. 2

Effects of PEG3350 + E in the extension phase. a Mean frequency of SBMs and CSBMs. b SBM and CSBM responder rate. c Ratio of type of stool consistency (median) categorized using the Bristol stool form scale [1, 2], [3, 4, 5], and [6, 7]. d Ratio of stool consistency (weekly median) at baseline and in the extension phase. BM bowel movement, CSBM complete spontaneous bowel movement, PEG3350 + E polyethylene glycol 3350 plus electrolytes, SBM spontaneous bowel movement. Baseline mean was based on week 2 in the run-in period. CSBMs were defined as SBMs with a sense of complete evacuation. Responders were defined as patients with 3 or more BMs and an increase of at least 1 BM per week from baseline

Fig. 3

PEG3350 + E and rescue medication use in the extension phase. a Mean and median number of weekly sachets. b Ratio of rescue medication use. PEG3350 + E polyethylene glycol 3350 plus electrolytes. Baseline mean was based on week 2 in the run-in period

Fig. 4

Other post hoc analyses. a Time zone ratio of SBM in the run-in period compared with the extension phase. b Individual data for treatment suspension as a result of improvement. Y-axis shows data for each patient. SBM spontaneous bowel movement