The primary objective of this study was to demonstrate bioequivalence between the novel calcium acetate oral solution (Phoslyra) and PhosLo Gelcaps in healthy volunteers with respect to serum P levels and urinary calcium (Ca) excretion.
The study was designed as a randomized, controlled, 3-arm open-label, cross-over Phase I study to demonstrate the bioequivalence of Phoslyra to PhosLo Gelcaps in healthy subjects.
The treatment sequences were ABC, BCA, and CAB, where A was Phoslyra, B was PhosLo Gelcaps, and C was calcium citrate (Figure 1).
Study medication dosages with each meal were 30 mL Phoslyra (667 mg calcium acetate per 5 mL), six PhosLo Gelcaps (667 mg calcium acetate/Gelcap), and five-5 calcium citrate caplets (950 mg calcium citrate/caplet), resulting in a daily dose of 90 mL Phoslyra and 18 PhosLo Gelcaps.
Sample size calculation was based on the 2-period, 2-sequence crossover design, since the comparison of primary interest was between liquid PhosLo and PhosLo Gelcaps.
Analysis for the two primary endpoints showed that Phoslyra was bioequivalent to PhosLo Gelcaps based on the 90% CIs of serum phosphorus ratios for Cmax and AUC0-6 (Table 3), and urinary Ca with Phoslyra was not more than that with PhosLo Gelcaps, as the 90% CIs of ratios for Rmax and Ae0-6 were within the upper bound of 125% (Table 4).
However, the lower values of the 90% CIs for Rmax and Ae0-6 fell below the lower bound of 80%, indicating that the Phoslyra cohort excreted less urinary P than the PhosLo Gelcaps (Table 5).
However, Cmax and mean insulin concentration following the Phoslyra treatment, while not significantly different, were 17% and 11% lower, respectively, compared to PhosLo Gelcaps.
The present study evaluated the bioequivalence between Phoslyra and PhosLo Gelcaps.
Figure 3) Comparisons of urinary excretion of Ca between the calcium acetate oral solution and PhosLo Gelcaps did not demonstrate traditional bioequivalence.
Of the secondary endpoints, strict bioequivalence was demonstrated for serum Ca between Phoslyra and PhosLo Gelcaps.