We present an application of a quantitative systems pharmacology (QSP) model to support a regulatory decision, specifically in assessing the adequacy of the proposed dosing regimen. On January 23, 2015, the US Food and Drug Administration (FDA) approved Natpara (human parathyroid hormone (PTH)) to control hypocalcemia in patients with hypoparathyroidism. Clinical trial results indicated that although once-daily PTH reduced calcium and vitamin D dose requirement while maintaining the normocalcemia, the regimen was not adequate to control hypercalciuria. We hypothesized that the lack of control on urinary calcium excretion was due to the short half-life of PTH. The QSP model-based simulations indicated that a more frequent dosing regimen may provide better control on hypercalciuria while maintaining normocalcemia. A postmarketing trial was recommended to assess pharmacokinetics (PKs) and pharmacodynamics (PDs) of PTH dose and dosing regimen. Although other modeling approaches may be feasible, in this specific case, QSP model-based simulations fulfilled the information gap to support recommendations of this postmarketing trial.
Published 2018. This article is a U.S. Government work and is in the public domain in the USA.