Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study

Abstract

Background: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dL.

Methods: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline P >5.5 mg/dL and ≤10.0 mg/dL, or were PB-naive with baseline P >4.5 mg/dL and ≤10.0 mg/dL, were included in OPTIMIZE. Participants taking PBs at baseline were randomized to switch from PBs to tenapanor (Straight Switch; n = 151) or reduce PB dosage by ≥50% and add tenapanor (Binder Reduction; n = 152); PB-naive patients started tenapanor alone (Binder-Naive; n = 30). Participants received tenapanor 30 mg twice a day for 10 weeks (part A), followed by an elective, 16-week open-label extension (part B). Outcomes included changes from baseline in P, intact fibroblast growth factor 23 (iFGF23), parathyroid hormone (PTH), serum calcium, and medication burden; patient-reported outcomes; and safety.

Results: By part A endpoint, 34.4% (Straight Switch), 38.2% (Binder Reduction), and 63.3% (Binder-Naive) of patients achieved P ≤5.5 mg/dL. Mean P reduction and median pill burden reduction from baseline to part A endpoint were 0.91± 1.7 mg/dL and 4 pills/day for the Straight Switch and 0.99± 1.8 mg/dL and 1 pill/day for the Binder Reduction group. The mean P reduction for Binder-Naive patients was 0.87± 1.5 mg/dL. Among Straight Switch and Binder Reduction patients who completed patient experience questionnaires, 205 of 243 (84.4%) reported an improved phosphate-management routine. Diarrhea was the most common adverse event (133 of 333 [39.9%]).

Conclusions: Tenapanor as monotherapy or in combination with PBs effectively lowered P toward the target range in patients who were PB naïve or who were not at goal despite PB use.

Funding: Ardelyx, Inc.

Trial registration: NCT04549597.