Abstract: TH-PO1048

VS-505: A Novel Phosphate Binder: First Clinical Experience in Haemodialysis Patients

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

  • Rosman, Johan, Curtin University, Perth, Western Australia, Australia
  • Asao, Testuji, KDL Inc., Tokyo, Japan
  • Thomas, Mark AB, Royal Perth Hospital, Perth, New South Wales, Australia
  • Yamauchi, Shitotomo, Ethic Co., Ltd., Chiyoda, TOKYO, Japan
Background

Phosphate binders (PB) side effects lead to non-compliance. Recently, iron-based PB were introduced, but absorption leads to high iron levels. VS-505 is a novel class PB where the iron ion (as ferric chloride) is bound to inert Arabic Gum. Animal studies showed superior efficacy and better tolerance without change in serum iron levels. This is the first study in haemodialysis patients to test safety, efficacy and tolerability.

Methods

This single arm, open label, dose escalation study used VS-505 in haemodialysis patients, stable on treatment for over 12 weeks. Plasma phosphate (Pi) level had to be between 6 - 10 mg/dl after a 2 weeks wash out from current PB. Other treatment, and dialysis modality remained unchanged. Treatment with VS-505 was 8 weeks with 2-weekly dose escalations, guided by Pi levels, from 1.5 g/day to 9.0 g/day. From screening to treatment day 22, lab parameters were followed weekly, then fortnightly. Primary Efficacy Endpoint was the Pi change during treatment. Secondary Efficacy Endpoints were Time Course of Pi to end of treatment and Plasma Calcium (Ca) change. Other criteria were trajectory of Iron Parameters, standard dialysis bloodtests, and Electro-Cardiograms. Tolerability was evaluated with questionnaires. Endpoints analysis by Intention to Treat/Full Analysis Set and a Per Protocol Set. A last Observation Carried Forward was applied for patients not completing the study.

Results

Sixteen patients were enrolled. 11 withdrew consent: 3 for diarrhea after dose escalation, 8 for medication-unrelated AE's. 30% of all patients reported black stools (iron). Only one subject received full dose escalation to 9 g/day, 4 reported abdominal dyscomfort after the escalation to 4.5 g/day.No changes of iron parameters were found. Routine parameters remained unchanged.
Plasma Pi was significantly reduced in the treatment group, median Pi change -2.40 mg/dl (-30.9%), (p<0.0001). Significant lowering of Pi levels were already observed at the lowest given dose of VS-505. There was no change of Ca levels, but a significant reduction in iPTH over the treatment period.

Conclusion

VS-505 is a promising, effective, safe and well-tolerated PB for the treatment of hyperphosphatemia with advantages over current drugs. Further studies in larger numbers of patients are warranted to find its exact place in routine treatment.

Funding

  • Commercial Support