OPC 41061 IN HOSPITALIZED PATIENTS W/ HYPONATREMIA

目前低钠血症的治疗选择是限水。这种疗法是有效的，但由于口渴的显著刺激而导致生活质量差。 本研究旨在证明每日口服药物纠正患者低钠血症并维持患者正常钠血症的能力。本研究的主要目的是评估固定维持剂量的OPC-41061在研究滴定阶段后低钠血症已纠正的患者中的疗效，并评估OPC-41061在研究各阶段的安全性。 本研究的次要目的是评估OPC-41061在低钠血症患者中诱导正常血清钠浓度的能力，并确定OPC-41061对血清钠浓度的剂量反应特征。OPC-41061是一种苯并氮杂卓衍生物，是由大冢制药公司开发的特异性和选择性的加压素V2肾亚型受体的非肽类拮抗剂。本研究是一项非肽类血管加压素V2受体拮抗剂OPC-41061治疗正常血容量或高血容量状态下低钠血症的多中心、随机、开放标签、活性对照、剂量滴定研究。 患者将在研究第0天至研究第14天在GCRC住院，并可在研究第14天评估后出院。志愿者将向GCRC单位报告，并将在第0天随机分配至活性药物组和安慰剂组，但所有患者将在研究第0天和第1天接受安慰剂治疗。 在第0天和第1天，将测量血清钠浓度。 将从GCRC厨房为每例受试者提供无添加盐的标准化饮食，并将严格监测和记录液体摄入和排出。 在安慰剂/研究药物给药后的前4小时内，活动将限于轻度活动。 在这4小时内，患者不应行走或站立超过45分钟。 饮水量将限制在最大1000 ml/天。 将记录尿液测量值和排出量。滴定住院期（研究第2天至<14天）：在第2-14天，受试者将接受单片研究药物或安慰剂与200 cc水。在所有研究日，从前一天午夜开始，患者将仅禁食。 在研究第2-14天给药后4小时内不进食。 应首先给予OPC-41061的最低剂量，并在随后的几天使用递增的更高剂量继续给药。 将每天进行钠测量、生命体征、实验室检查和ECG。 将严格保持液体摄入和输出监测。门诊阶段（研究第15至28天）：和随访阶段（研究第35和65天）：患者将继续以出院时给药的剂量（或体积）接受每日剂量的OPC-41061（或液体限制和安慰剂）。 出院后，将每隔一天进行一次生命体征、体温和体重、实验室检查和ECG检查。 随访访视将在第35天和第65天进行，届时将进行生命体征、实验室检查、ECG和口渴量表。由于所有研究中心的加速缓慢，申办者已终止该计划。

The current treatment of choice for hyponatremia is water restriction. This therapy is effective but results in a poor quality of life due to significant stimulation of thirst. This study is intended to demonstrate the ability of a daily oral agent to correct a patient's hyponatremia and maintain the patient at normonatremia. The primary objective of this study is to assess the efficacy of a fixed, maintenance dose of OPC-41061 in patients whose hyponatremia has been corrected following the titratioin phase of the study, and to assess the safety of OPC-41061 in each phase of the study. The secondary objectives of the study are to assess the ability of OPC-41061 to induce a normal serum sodium concentration in hyponatremic patients and to determine dose-response characteristics of OPC-41061 on serum sodium concentration. OPC-41061, a benzazepine derivative, is a specific and selective, nonpeptide antagonist of the vasopressin V2 renal subtype receptor, developed by Otsuka Pharmaceutical Company. The study is multi-center, randomized, open-label, active-controlled, dose titration study of a non-peptide vasopressin V2-receptor antagonist, OPC-41061, for the treatment of hyponatremia in euvolemic or hypervolemic states. Patients will be hospitalized in the GCRC on Study Day 0 through Study Day 14 and may be discharged after evaluation on Study Day 14. The volunteers will report to the GCRC unit and will be randomized at Day 0 between the active and the placebo groups, but all patients will receive placebo on study days 0 and 1. On days 0 and 1, serum sodium concentration will be measured. Each subject will be given a no added salt standardized diet from the GCRC kitchen and fluid intake and output will be strictly monitored and recorded. Activity will be restricted to light activity for the first 4 hours after placebo/study drug administration. Patients should not walk or stand for more than a total of 45 minutes during this 4 hour period. Water intake will be limited to a maximum of 1000 ml/day. Urine measurements and output will be recorded. Titration Inpatient Phase (study days 2 to <14): On days 2-14, subjects will receive a single tablet of Study Drug or placebo with 200 cc of water. Patient will be fasting from food only, from midnight the night before on all study days. No meal will be served until 4 hours post-dose on Study Days 2-14. The lowest dose of OPC-41061 shall be given first and will continue on subsequent days using incrementally higher doses. Sodium measurements, vital signs, laboratory tests and ECG will be performed daily. Fluid intake and output monitoring will be strictly maintained. Outpatient Phase (study days <15 to 28): and Follow-Up Phase (study days 35 and 65): The patient will continue to receive daily doses of OPC-41061 (or fluid restriction and placebo) at the dose (or volume) administered at discharge. After discharge, every other day, vital signs, temperature and weight, laboratory tests, and ECG will be performed. Follow-Up visits will occur on Days 35 and 65 when vital signs, laboratory tests, ECG and thirst scale will be performed. Due to slow accrural at all sites, this projected has been terminated by the sponsor.