Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial

Abstract

Background: Tenapanor is a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis.

Methods: This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5-7.0 mg/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint.

Results: Of the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was - 1.18 mg/dL (95% confidence interval: - 1.54, - 0.81 mg/dL) with tenapanor. From a baseline value of 7.65 mg/dL, serum phosphorus decreased to 6.14 and 5.44 mg/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5-6.0 mg/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%.

Conclusions: Administration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable.

Trial registration: NCT04766385.

Keywords: CKD-MBD; Chronic kidney disease; Hyperphosphatemia; NHE3 transporter; Peritoneal dialysis; Tenapanor.

Fig. 1

Study design. PD peritoneal dialysis

Fig. 2

Patient disposition. BSFS Bristol Stool Form Scale, ECG electrocardiogram, PD peritoneal dialysis

Fig. 3

a Time course of serum phosphorus levels over time in the mITT and b change from baseline in serum phosphorus level over time. Patients who discontinued on the same day as the specified visit were included in the results of each visit. Some patients received additional phosphate binders. mITT, modified intention-to-treat population

Fig. 4

a Time course of the mean dose of tenapanor and b changes in the dose distribution of tenapanor. EOT end of treatment

Fig. 5

Proportion of patients achieving target serum phosphorus level of 3.5–6.0 mg/dL over time. EOT end of treatment

Fig. 6

Change from baseline in a calcium × phosphorus (Ca × P) and b serum corrected calcium. EOT end of treatment

Fig. 7

Change from baseline in a intact FGF23 and b iPTH. EOT end of treatment, FGF23 fibroblast growth factor 23, iPTH intact parathyroid hormone

Fig. 8

Change in mean a Bristol Stool Form Scale (BSFS) score and b stool frequency per week over time