Aims:
Bowel preparations contain electrolytes to maintain electrolyte homeostasis after
diarrhoea. This post-hoc analysis of randomised, Phase 3 clinical trials assessed
plasma sodium concentrations following treatment with the 1L NER1006.
Methods:
The safety of NER1006 was assessed in the studies NOCT, MORA and DAYB. This analysis
included patients whose plasma sodium concentrations shifted from normal at baseline
to above upper limit normal (ULN) at any subsequent visit. ULN was defined locally
and ranged from 143 – 148mmol/L. Timing of blood sample collection was determined
by the dosing schedule. Samples were collected at 4 visits: at baseline (1), day of
colonoscopy (2), 1 – 4 days (3) and 8 – 10 days (4) post-colonoscopy.
Results:
Among 1134 randomised patients, 1028 had evaluable sodium data and 214 were included
in this analysis (Table). A transient shift around 5mmol/L occurred predominantly
at Visit 2, with 96.4 – 99.6% patients returning to normal levels by visit 3. More
patients in NOCT compared to MORA and DAYB experienced elevated sodium levels. However,
in NOCT the baseline value was high with > 50% patients at > 142mmol/L. For such patients,
minor shifts of only 2 – 3mmol/L would exceed ULN. There were 4 reported cases of
mild hypernatremia across the studies, all of which were considered treatment-related
by investigator. No hyponatraemia was observed with NER1006. Across all three studies
the median changes in plasma electrolyte levels were transient and not considered
clinically significant.
Tab. 1:
Mean sodium plasma levels in NER1006 patients who were normal at baseline but above
ULN at subsequent visit (safety set).
|
Study % patients with shift Normal baseline to ULN
|
Baseline Mean mmol/L (SD)
|
Visit 2 Mean mmol/L (SD)
|
Visit 3 Mean mmol/L (SD)
|
Visit 4 Mean mmol/L (SD)
|
|
MORA (n = 92) 17% (92/531)
|
142 (2.08)
|
148 (2.05)
|
142 (2.83)
|
143 (2.56)
|
|
DAYB (n = 17) 7% (17/235)
|
141 (1.87)
|
146 (2.26)
|
144 (2.68)
|
143 (2.62)
|
|
NOCT (n = 105) 40% (105/262)
|
141 (1.82)
|
147 (1.61)
|
142 (2.23)
|
142 (2.06)
|
|
Overall (n = 214)
|
142 (1.96)
|
147 (1.92)
|
142 (2.57)
|
142 (2.35)
|
Conclusions:
Mild, transient increases in plasma electrolyte levels were observed with NER1006
(PLENVU) on visit 2, these were not clinically significant.
