Transient alterations in plasma sodium concentrations with NER1006 bowel preparation: an analysis of three phase III, randomized clinical trials

Abstract

Background: This analysis characterized changes in sodium levels in patients receiving the 1 L polyethylene glycol-based preparation NER1006.

Methods: Data were pooled from three phase III, randomized clinical trials. A post hoc subanalysis included adults who received a 2-day split-dose (evening/morning) NER1006 regimen, a 1-day split-dose (morning only) regimen, or evening-before regimen and had an increase in sodium concentrations from normal to above the upper limit of normal (143-148 mmol/L) at ≥ 1 of three post-treatment visits. Blood samples were collected at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4).

Results: A total of 214 of 1028 patients were included. Of the 214 patients, sodium concentration increased from a mean baseline value of 141.8 mmol/L to a mean of 147.1 mmol/L (median increase from baseline of approximately 5 mmol/L). The mean sodium concentration was within normal range at visit 3 (142.3 mmol/L) and visit 4 (142.4 mmol/L), as was the median sodium concentration. Overall, ~ 90% of patients had a normal serum concentration at visits 3 and 4. Based on day of colonoscopy test results, there were four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3.

Conclusion: NER1006 was associated with small, transient increases in sodium levels that were not considered clinically significant. Trial registration NOCT (ClinicalTrials.gov: NCT02254486 [registered October 2, 2014]), MORA (ClinTrials.gov: NCT02273167 [registered October 23, 2014]; EudraCT number: 2014-002185-78 [registered August 13, 2014]), DAYB (ClinicalTrials.gov: NCT02273141 [registered October 23, 2014]; EudraCT Number: 2014-002186-30 [registered August 12, 2014]).

Keywords: Colonoscopy; NER1006; Plenvu; Polyethylene glycol; Sodium.

Conflict of interest statement

BDC reports serving as a consultant and speaker for Salix Pharmaceuticals. CA is an employee of Salix Pharmaceuticals. DMP reports serving as a consultant and educator for Olympus Medical; and serving as a consultant for Salix Pharmaceuticals.

© 2022. The Author(s).

Figures

Fig. 1

Patient populations. *All patients randomly assigned to treatment for whom patient diary data could not rule out that they received at least one dose of NER1006. †Patients included in the safety population who had a normal sodium concentration at baseline and an increase from baseline to above the upper limit of normal (ULN) for sodium (143–148 mmol/L). ‡Reported as an adverse event based on test results on the day of colonoscopy; medical intervention was not required, and sodium levels returned to normal range within 2 ± 1 days post-colonoscopy. DAYB Day Before Arm MORA Morning Arm NOCT Nocturnal Pause Arm

Fig. 2

Box and whisker plots of a median and b change from baseline in median sodium concentrations. Values were determined at baseline, day of colonoscopy (visit 2), 2 ± 1 days post-colonoscopy (visit 3), and 7 ± 1 days post-colonoscopy (visit 4). Box shows median, and upper and lower quartile values; whisker designates upper and lower values. Circles in graph represent outliers. DAYB Day Before Arm MORA Morning Arm NOCT Nocturnal Pause Arm