Kidney Week

Abstract: FR-OR033

EOS789, a Novel Pan-Inhibitor of NaPi-IIb/PiT-1/PiT-2, Decreased Intestinal Phosphate Absorption in Hemodialysis Patients Measured by Sensitive and Direct Method Using 33P: A Phase 1b Clinical Trial

Session Information

• Bone and Mineral Metabolism: Clinical Research
  November 08, 2019 | Location: 145, Walter E. Washington Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Moe, Sharon M., Indiana University, Indianapolis, Indiana, United States

Sharon M. Moe, MD, FASN



Dr. Sharon Moe is the Stuart A. Kleit Professor of Medicine and Director of the Division of Nephrology at Indiana University School of Medicine in Indianapolis, Indiana. She is a Past President of the ASN.

• Trevino, Laurie, Indiana University, Indianapolis, Indiana, United States

Laurie Trevino,

• Moorthi, Ranjani N., Indiana University, Indianapolis, Indiana, United States

Ranjani N. Moorthi,

• Doshi, Simit, Indiana University, Indianapolis, Indiana, United States

Simit Doshi,

• Wastney, Meryl E., Metabolic Modeling Services, Blenheim, New Zealand

Meryl E. Wastney,

• Hisada, Nozomi, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Nozomi Hisada,

• Kake, Takei, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Takei Kake,

• Ogita, Yoshitaka, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Yoshitaka Ogita,

• Fujii, Naohisa, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Naohisa Fujii,

• Matsuda, Yuya, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Yuya Matsuda,

• Sato, Jotaro, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan

Jotaro Sato,

• Hill Gallant, Kathleen M., Purdue University, West Lafayette, Indiana, United States

Kathleen M. Hill Gallant,

Background

Elevated serum phosphorus (P) remains problematic in dialysis patients. EOS789, a novel pan-phosphate transporter inhibitor (NaPi-IIb, PiT-1, PiT-2), showed increased fecal phosphate excretion in healthy subjects in phase 1 study. Here we report safety and efficacy of EOS789 in hemodialysis (HD) patients (pts).

Methods

We conducted two cross-over, randomized sequence studies of identical design. The first compared EOS789 50 mg to placebo tid with meals. The second compared EOS789 100 mg vs EOS789 100 mg + 1600 mg sevelamer carbonate tid with meals. Pts undergoing thrice weekly HD, with a rise in serum P of 0.5 mg/dL after 15-19 days without a phosphate binder were eligible. Pts consumed a standardized diet containing 900 mg of P for 2 weeks. Study drug was given on days 4 to 14 with the diet. On day 10 subjects were admitted to the CRC for 3 days. Pts had pre-dialysis blood drawn, dialysis treatment, a meal with an oral dose of 10 uCi of 33P, and the next day they received 10 uCi 33P by IV. Serial blood draws were taken over 48h post-oral 33P dose, serum was analyzed for 33P activity, and percent P absorption was determined by kinetic modeling.

Results

A total of 12 to 14 patients were randomized to each study; 10 completed all assessments. There were no study drug related SAEs. Eight patients had gastrointestinal disorders (2 patients in each group). For efficacy, percent P absorption was 56% for placebo vs. 51% for EOS 50 mg (p=0.52) and 40% for EOS 100 mg vs. 36% for EOS 100 mg + sevelamer (p=0.45). Within each individual cross over study, these differences did not reach significance. When the 6 pts that completed both studies awere analyzed, percent P absorption was significantly lower with EOS 100 mg (44%) compared with placebo (63%) (p=0.013) and trended lower compared with EOS 50 mg (55%, p=0.12).

Conclusion

In this phase 1b study in HD pts, EOS789 was well tolerated. There was a significant decrease in intestinal P absorption at EOS789 100 mg tid. Importantly, 33P is a sensitive and direct measure of intestinal absorption, and is a superior method to serum P that is confounded by dialysis P clearance and bone remodeling.