Supplementary Material for: Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis

<p><b><i>Background:</i></b> Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. <b><i>Methods:</i></b> Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks. Phosphate (P) binders were discontinued on admission. Patiromer, 12.6 g daily (divided 4.2 g TID with meals), was started on the Monday morning following the last pretreatment week blood sampling. Serum and 24-hour stool samples were collected daily. <b><i>Results:</i></b> Mean ± SE serum K decreased (maximum change per corresponding day, 0.6 ± 0.2 mEq/l, p = 0.009) and fecal K increased 58% on patiromer compared with the pretreatment week. During the pretreatment week, 69.0, 47.6, and 11.9% of patients' serum K values were ≥5.5, ≥6.0, and ≥6.5 mEq/l, respectively. This was reduced to 38.1% (p = 0.009), 11.9% (p < 0.001), and 2.4% (p = 0.2) on patiromer. Following P binder discontinuation, the long interdialytic interval mean ± SE serum P numerically increased from 5.8 ± 0.4 to 7.0 ± 0.5 mg/dl (p = 0.06). On patiromer, P decreased from 7.0 ± 0.5 to 6.2 ± 0.5 mg/dl (p = 0.04). While on patiromer, fecal P numerically increased by 112 ± 72 mg/day (17%; p = 0.1792; range -148 to 344 mg/day). No patient discontinued patiromer because of adverse events (AEs); none had serious AEs. <b><i>Conclusions:</i></b> In 6 hyperkalemic HD patients, patiromer decreased serum K and P levels and increased fecal K.</p

Supplementary Material for: Treatment of Secondary Hyperparathyroidism: Results of a Phase 2 Trial Evaluating an Intravenous Peptide Agonist of the Calcium-Sensing Receptor

<p><b><i>Background/Aims:</i></b> This study evaluated the efficacy and safety of AMG416 (etelcalcitide), a novel peptide agonist of the calcium (Ca)-sensing receptor given intravenously (IV) after each hemodialysis session for the treatment of secondary hyperparathyroidism (SHPT). <b><i>Methods:</i></b> Adult subjects with SHPT on hemodialysis enrolled in a 12-week, dose titration (parent) study followed by an open-label extension phase. AMG416 was administered IV, thrice weekly starting at 5 mg/session and titrated based on the subject's parathyroid hormone (PTH) and albumin-corrected Ca (cCa) to target a PTH of 150-300 pg/ml. Efficacy (percent PTH change from baseline to the efficacy analysis period during the parent study) and safety (open-label extension phase) endpoints were evaluated. <b><i>Results:</i></b> Baseline (n = 37) mean (standard error [SE]) PTH was 853 (106 pg/ml). The mean (95% CI) percent change from baseline to the efficacy analysis period in PTH concentration was -53.6% (-60.8, -46.4). The proportion of subjects with ≥30% reduction in PTH from baseline to the efficacy assessment period (EAP) was 89% (32/36; 95% CI 73.9, 96.9). Results by the baseline PTH subgroup (≤700 vs. >700 pg/ml) were comparable for both analyses. The proportion of subjects achieving a PTH ≤300 pg/ml was 56% (n = 20/36) at the efficacy assessment period. The mean (SE) percent changes from baseline to EAP were observed for cCa -15% (1.0%) and phosphorus -10% (3.3%). Adverse events were mild to moderate in severity. The PTH reductions achieved in the parent study were maintained in the open-label extension phase. <b><i>Conclusion:</i></b> AMG416 was well tolerated and appears to be an effective agent for the treatment of SHPT in patients on hemodialysis.</p