AJKD recently published an article from Dwyer et al on a dose-response and safety/tolerability trial of a novel phosphorous binder, ferric citrate, for dialysis patients. This trial demonstrated lower serum phosphorus levels with increasing dose. (The same group is currently conducting a pivotal phase three trial comparing this compound to currently available phosphorus binders.) Dr. Jamie Dwyer (JD) spoke about the AJKD dose-response article with Dr. Joel Topf (eAJKD), eAJKD Advisory Board member.
eAJKD: Can you tell us about this study on a novel, iron-based, phosphate binder?
JD: Ferric compounds have been studied in humans for several years now. Ferric citrate was demonstrated to have efficacy on kidney outcomes in prior trials. We wanted to demonstrate and clarify the dose-response relationship for this agent in end-stage renal disease patients. We think that dialysis patients need alternatives to their binders as many of the current binders have gastrointestinal side effects.
eAJKD: The doses for ferric citrate used were one, six, and eight grams. Why were the dose comparisons not more spread out?
JD: At the time the trial design, eight grams was the maximum dose that had been administered to humans. The trial required a low-, mid-, and high-dose to demonstrate a dose-effect relationship: the goal of the trial.
eAJKD: Why are none of the doses divisible by three, like most other phosphate binders?
JD: Three equal doesn’t reflect how some people eat. Across all of the ferric citrate projects, we have been allowing the local investigator to recapitulate real-life more closely. Physicians can dose ferric citrate however they want, as long as the total dose is delivered. This allows the participant and his or her physician to customize dosing based on their eating habits.
eAJKD: The study enrolled less than half the people that you screened. Any reason why?
JD: This is because some subjects had phosphorus levels that didn’t rise high enough during the washout. We don’t talk about the nutritional status of our dialysis patients as much as we should in our community. Many patients don’t eat as much as we think they might be eating. A reflection of that is phosphorus levels don’t get dangerously high when you stop their phosphate binders.
eAJKD: Looking at the adverse events, it appears ferric citrate is very well tolerated. Besides the stool color change, were there any other significant adverse events?
JD: We remain surprised that not everyone noticed that the stool turns black. No other adverse events were significant. In terms of stool color, this limited patient blinding in this study. In fact, we chose not to make these pivotal trials blinded—this is an open label study. Patients knew they got randomized to the drug because their stool turned black.