A Phase 1 dose-ranging study examining the effects of a superabsorbent polymer (CLP) on fluid, sodium and potassium excretion in healthy subjects

Lee W Henderson, Howard C Dittrich, Alan Strickland, Thomas M Blok, Richard Newman, Thomas Oliphant, Detlef Albrecht, Lee W Henderson, Howard C Dittrich, Alan Strickland, Thomas M Blok, Richard Newman, Thomas Oliphant, Detlef Albrecht

Abstract

Background: CLP is an orally administered, non-absorbed, superabsorbent polymer being developed to increase fecal excretion of sodium, potassium and water in patients with heart failure and end-stage renal disease. This study was conducted to evaluate the safety of CLP, and to explore dose-related effects on fecal weight, fecal and urine sodium and potassium excretion, and serum electrolyte concentrations.

Methods: This Phase 1, open-label, dose-escalation study included 25 healthy volunteers, who were administered CLP orally immediately prior to four daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An additional dose group received 15.0 g/day CLP under fasting conditions, and an untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary output was collected daily. Samples were weighed, and sodium, potassium, and other ion content in stool and urine were measured for each treatment group. Effects on serum cation concentrations, other standard laboratory values, and adverse events were also determined.

Results: At doses below 25.0 g/day, CLP was well tolerated, with a low frequency of self-limiting gastrointestinal adverse events. CLP increased fecal weight and fecal sodium and potassium content in a dose-related manner. Concomitant dose-related decreases in urinary sodium and potassium were observed. All serum ion concentrations remained within normal limits.

Conclusions: In this study, oral CLP removed water, sodium and potassium from the body via the gastrointestinal tract in a dose related fashion. CLP could become useful for patients with fluid overload and compromised kidney function in conditions such as congestive heart failure, salt sensitive hypertension, chronic kidney disease and end stage renal disease.

Trial registration: NCT01944007.

Figures

Figure 1
Figure 1
Daily fecal weight following 15.0 g/day CLP for 9 days under fed conditions. Values are means ± 95% confidence intervals. Blue line indicates start of steady state.
Figure 2
Figure 2
Mean (standard deviation) fecal weight by treatment group. Values are daily averages from Days 5-9, the time period reflective of steady state CLP exposure.
Figure 3
Figure 3
Mean (standard deviation) fecal content of sodium and potassium following CLP treatment and untreated control. Values are daily averages from Days 5-9, the time period reflective of steady state CLP exposure.
Figure 4
Figure 4
Mean (standard deviation) urine content of sodium and potassium following CLP treatment and untreated control. Values are daily averages from Days 5-9, the time period reflective of steady state CLP exposure.
Figure 5
Figure 5
Mean serum carbon dioxide (CO2) concentration for each treatment group by study day. Dashed lines represent the normal range (23-32 mmol/L).

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