Replace is a double-blind, placebo-controlled trial that will randomize approximately 110 patients at over a dozen sites in the US, Canada and Europe. The primary objective is to demonstrate, over a 24-week treatment period, that once-daily subcutaneous dosing with NPSP558 at doses of 50mcg, 75mcg or 100mcg is a safe and effective hormone replacement therapy for the treatment of patients with hypoparathyroidism.
The study will consist of a maximum 10-week screening and stabilization period followed by a 24-week treatment period marked by randomization (2:1) to NPSP558 50mcg (with the potential for titration up to 75mcg and 100mcg) or placebo.
Following randomization, patients will undergo staged reductions in calcium and vitamin D supplementation, while maintaining a serum total calcium within clinically stable limits. If needed, up-titration of study drug to 75mcg or 100mcg in patients over a six- to eight-week period will be performed. Patients will continue on their final NPSP558 dose through week 24 and a follow-up period will last from week 24 to week 28.
Efficacy will be demonstrated by achievement or maintenance of a normal or clinically acceptable stable albumin-corrected serum total calcium in parallel with reduced requirements for oral supplementation with calcium and treatment with active vitamin D metabolites or analogs.
NPSP558 is the company’s proprietary recombinant full-length human parathyroid hormone (PTH 1-84), which mimics the action of natural parathyroid hormone. NPS believes positive results from Replace will enable it to seek US marketing approval for NPSP558 for the treatment of hypoparathyroidism.
Francois Nader, president and CEO of NPS Pharmaceuticals, said: “We are encouraged by NPSP558’s activity to date and believe it has the optimal mechanism of action to address the significant needs of this underserved patient population. We expect to complete the study and report topline results in the second half of 2010.”