Vasopressin (AVP), the antidiuretic hormone, is a peptide hormone actively involved in the regulation of body fluid osmolality, blood volume, blood pressure, and cell proliferation via the stimulation of specific membrane-bound receptors classified into V1a-vascular, V2-renal, and V3-pituitary subtypes having distinct pharmacological profiles and intracellular second messengers. The secretion of AVP is an absolute requirement for the maintenance of fluid homeostasis as shown in human and experimental models of diabetes insipidus. The usefulness of natriuretic agents has been demonstrated in conditions associated with water and salt retention. However, there are diseases (hyponatremia of congestive heart failure, liver cirrhosis, nephrotic syndrome, and the syndrome of inappropriate secretion of antidiuretic hormone, SIADH) due to the inappropriate release of vasopressin and characterized by an excess retention of water. An agent that increases urine output by producing a free water diuresis would be of significant advantage in these conditions. Such agents have been coined """"""""aquaretics"""""""" before. Recently, selective non-peptidic orally active AVP antagonists have been developed; YM-087 being one of these compounds. The primary objective of this placebo-controlled double-blind study is to determine the dose-dependent effects (20 or 40 mg bid) of oral YM-087 on serum sodium in patients with euvolemic or hypervolemic hyponatremia. The secondary objective of the study is to assess the safety and tolerance of 2 dose levels of oral YM087 in patients with euvolemic or hypervolemic hyponatremia. The study is a multi-center, randomized, double blind, placebo controlled, parallel group, inpatient and outpatient study assessing the efficacy and safety of 5 days of treatment with oral YM-087 on serum sodium levels in patients with euvolemic or hypervolemic hyponatremia between 115 to <130 mmol/1.
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