In a phase 3 trial, tenapanor, an oral drug that acts via a non–phosphate-binding mechanism, significantly decreased elevated serum phosphate in patients with hyperphosphatemia receiving maintenance hemodialysis, investigators reported in the Journal of the American Society of Nephrology.
Geoffrey A. Block, MD, of the Denver Nephrology Research Division, Denver Nephrology, Denver, Colorado, and colleagues tested the safety and efficacy of tenapanor—a minimally absorbed inhibitor of gastrointestinal sodium/hydrogen exchanger 3 that reduces paracellular phosphate transport in the intestine—in a 2-phase trial. For the first phase, they randomly assigned patients to receive twice-daily oral tenapanor (3, 10, or 30 mg) for 8 weeks. In the second phase, they re-randomized patients to receive either their previously assigned dose or placebo for a 4-week “withdrawal” period.
Of 219 patients randomized, 152 completed both study phases. In the first phase, all 3 treatment groups had significant decreases in mean serum phosphate. The 3 mg dose led to a reduction of 1.0 mg/dL after 8 weeks of treatment. The 10 mg and 30 mg dose (down-titrated) resulted in a reduction of 1.02 and 1.19 mg/dL, respectively. In the second phase, tenapanor demonstrated significant benefits over placebo, with a mean increase of 0.02 mg/dL in the tenapanor recipients (pooled data) compared with a mean increase of 0.85 mg/dL in the placebo group.
“Adverse events were largely limited to softened stool and a modest increase in bowel movement frequency, resulting from increased stool sodium and water content, stemming from tenapanor’s mechanism of action,” the authors noted.
Block GA, Rosenbaum DP, Yan A, et al. and Efficacy and safety of tenapanor in patients with hyperphosphatemia receiving maintenance hemodialysis: A randomized phase 3 trial. J Am Soc Nephrol. 2019; published online ahead of print.