AMG 416 Safe after Discontinuation of Cinacalcet

San Diego—Significant decreases in parathyroid hormone (PTH) with no increase in serum phosphate or in albumin-adjusted serum calcium have been shown in two previous 26-week placebo-controlled randomized clinical trials with AMG 416, a novel intravenous calcimimetic agent.

Kenneth Liss, DO, and colleagues recently conducted a 4-week, multiple-dose single-arm, open-label safety study designed to assess the incidence of hypocalcemia in patients treated with intravenous AMG 416 following discontinuation of daily oral cinacalcet. The researchers reported results of the study during a poster session at Kidney Week 2015 in a poster titled Initiation of AMG 416 after Discontinuation of Cinacalcet.

The primary end point was hypocalcemia defined as albumin-adjusted serum calcium <7.5 mg/dL; the secondary end point was hypocalcemia defined as albumin-adjusted serum calcium <8.3 mg/dL. Enrolled patients were on a stable dose of daily oral cinacalcet (30, 60, or ≥90 mg) for at least 4 weeks before and during the 4 weeks of screening. Participants underwent a cinacalcet washout period of at least 7 days.

Participants who had a serum calcium ≥8.3 mg/dL during the washout period were treated with 5 mg AMG 416 after hemodialysis three times a week for 4 weeks, followed by a 4-week safety observation period. If a dose hold was required for low serum calcium or low parathyroid hormone (PTH), defined as two consecutive predialysis PTH <100 pg/mL, the dose of AMG 416 could be restarted at 2.5 mg during the treatment period. Increases in dose were not allowed.

Of the 158 enrolled participants, 148 completed the washout period and received AMG 416. Of the 148, 140 completed the 4-week treatment period.

The per-subject incidence of low serum calcium during the 4-week AMG 416 treatment period among participants who received a prior dose of 30 mg oral cinacalcet (n=63) was 0%  (n=0) among those with serum calcium <7.5 mg/dL and 28.6% (n=18) among those with serum calcium <8.3 mg/dL. In the group who received prior oral cinacalcet dose of 60 mg (n=47), the per-subject incidence was 2.1% (n=1) among those with serum calcium <7.5 mg/dl and 8.5% (n=4) among those with serum calcium <8.3 mg/dL. Among the group who received prior oral cinacalcet dose ≥90 mg, the incidence of hypocalcemia defined as <7.5 mg/dL was 0% (n=0) and the incidence of hypocalcemia defined as <8.3 mg/dL was 2.9% (n=1).

Post-baseline, no participant had albumin-adjusted serum calcium <7.0 mg/dL and no one developed symptomatic hypocalcemia. Four participants discontinued AMG 416 due to subject request and two discontinued due to adverse events. One subject was lost to follow-up and one due to death.

“Treatment with AMG 416 at a starting dose of 5 mg can be safely initiated after a 7-day washout of cinacalcet therapy, provided that [albumin-adjusted serum calcium] is ≥8.3 mg/dL,” the researchers said.

Source: Liss K, Block GA, Chertow GM, Dehmel B, Sun Y, Spiegel DM. Initiation of AMG 416 after discontinuation of cinacalcet. Abstract of a poster presented during American Society of Nephrology Kidney Week 2015, November 5, 2015, San Diego, California.

Funding for this study was provided by Amgen.