US-based NPS Pharmaceuticals has started a Phase IIa trial to assess the safety and tolerability of an intravenous (IV) infusion of NPSP795, a selective calcium receptor antagonist, in adult patients with autosomal dominant hypocalcemia (ADH).
ADH is an ultra-rare genetic disorder of calcium homeostasis caused by mutations in the calcium-sensing receptor (CaSR) gene that increase the sensitivity of the receptor to serum calcium.
NPSP795 binds to the CaSR and decreases its sensitivity to serum calcium. Its mechanism of action restores the normal physiological action of the CaSR and addresses the underlying molecular defect in ADH to return to normal calcium homeostasis.
The company intends to announce preliminary top-line data from the Phase IIa trial later this year or in early 2015.
NPS Pharma executive vice-president and chief medical officer Roger Garceau said: "NPS Pharma is committed to advancing the understanding of autosomal dominant hypocalcemia (ADH), an ultra-rare genetic disease that can lead to serious renal complications.
"This new study is an important step in our exploration of the potential of NPSP795 for the treatment of patients with ADH, who do not have approved treatment options."
The non-randomised, open-label, dose-escalating trial will also evaluate the ability of various doses of NPSP795 to stimulate parathyroid hormone secretion, increase blood calcium and decrease renal calcium excretion.
A total of 12 patients will be enrolled in the trial at the National Institute of Health's clinical centre in Bethesda, Maryland, US.
The underlying cause of symptoms and complications in patients with ADH are two-fold.
First, absolute hypocalcemia can cause life-threatening seizures, laryngeal spasms, cardiac arrhythmias, tetany, paresthesias, muscle cramping and decreased focus.
In addition, the body's perceived hypercalcemia results in inappropriately increased renal calcium excretion, decreased renal phosphate excretion, and hyperphosphatemia, putting patients at risk for renal complications, including renal stones, nephrocalcinosis and impaired renal function, as well as soft tissue calcifications.
The company is currently focusing on therapeutic areas of gastrointestinal disease and endocrine disorders, which include short bowel syndrome, hypoparathyroidism and ADH.