The FDA approval of Natpara was based on a 24-week, randomized, double-blind, placebo-controlled, multicenter trial. In this trial, patients with established hypoparathyroidism receiving calcium and active forms of vitamin D (vitamin D metabolite or analogs) were randomized to Natpara (n=84) or placebo (n=40). Before randomization, participants entered a 2-16 weeks run-in phase. In this phase calcium supplement and active vitamin D doses were adjusted to target an albumin-corrected serum calcium concentration between 8.0 and 9.0 mg/dL and 25-hydroxyvitamin D was replaced in patients with insufficient stores. At randomization, baseline serum calcium was 8.6 mg and participants were receiving a median (interquartile range) daily oral calcium dose of 2000 (1250, 3000) mg and a median daily oral activevitamin D dose equivalent to 0.75 mcg (0.5, 1) of calcitriol. At randomization, active forms of vitamin D were reduced by 50% and patients were randomized to Natpara 50 mcg daily or placebo. Randomization was followed by a 12-week Natpara titration phase and a 12-week Natpara dose maintenance phase. During the titration phase Natpara was increased by 25 mcg increments every four weeks up to a maximum of 100 mcg. Titration was indicated for patients who could not achieve independence from active vitamin D and who could not reduce oral calcium to 500 mg or less per day. At end of treatment, 56% of subjects randomized to Natpara were receiving 100 mcg of Natpara per day, 26% were receiving 75 mcg of Natpara per day, and 18% were receiving 50 mcg of Natpara per day. Doses of co-administered active forms of vitamin D and calcium were adjusted (reduced or increased) to maintain albumin-corrected serum calcium within a desired target range throughout the trial in both arms. For the efficacy analysis, subjects that fulfilled three components of a three-part response criterion were considered responders. A responder was defined as an individual who had: at least a 50% reduction from baseline in the dose of active vitamin D, at least a 50% reduction from baseline in the dose of oral calcium supplementation and an albumin-corrected total serum calcium concentration between 7.5 mg/dL and 10.6 mg/dL. At the end of treatment, significantly (p-value