OPC 41061 IN HOSPITALIZED PATIENTS W/ HYPONATREMIA

OPC 41061 用于低钠血症住院患者

• 批准号: 6264424
• 负责人: MARC THIBONNIER
• 金额: $ 1.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264424
• 关键词: benzazepines; clinical research; dosage; drug adverse effect; drug screening /evaluation; human subject; human therapy evaluation; hyponatremia

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.

目前治疗低钠血症的首选方法是限水。这种疗法是有效的，但由于口渴的显著刺激导致生活质量差。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在研究滴定期后已纠正低钠血症的患者中的疗效，并评估OPC-41061在研究的每个阶段的安全性。该研究的次要目的是评估OPC-41061诱导低钠血症患者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是一种苯氮平衍生物，是大冢制药公司开发的抗利尿激素V2肾亚型受体的特异性和选择性非肽拮抗剂。该研究是一项多中心、随机、开放标签、主动控制、剂量滴定的非肽抗利尿素v2受体拮抗剂OPC-41061的研究，用于治疗低血容量或高血容量状态的低钠血症。患者将在研究第0天至研究第14天在GCRC住院，并可能在研究第14天评估后出院。志愿者将向GCRC单位报告，并将在第0天随机分为活性组和安慰剂组，但所有患者将在研究第0和第1天接受安慰剂。在第0天和第1天，测定血清钠浓度。每位受试者将从GCRC厨房获得无添加盐的标准化饮食，并严格监控和记录液体摄入和排出。在服用安慰剂/研究药物后的头4小时内，活动仅限于轻度活动。在这4小时内，患者走路或站立的时间不应超过45分钟。饮水量限制在每天最多1000毫升。记录尿量和尿量。住院期（研究第2天至<14天）：在第2-14天，受试者将服用一片研究药物或安慰剂，并加入200cc水。在所有学习日，患者将从前一天午夜开始禁食。在第2-14天的给药后4小时将不提供膳食。应首先给予最低剂量的OPC-41061，并在随后的几天继续使用逐渐增加的剂量。每天进行钠测量、生命体征、实验室检查和心电图检查。严格监控液体的摄入和排出。门诊期（研究天数<15至28天）和随访期（研究天数35至65天）：患者将继续接受出院时剂量（或体积）每日剂量的OPC-41061（或液体限制和安慰剂）。出院后，每隔一天检查一次生命体征、体温、体重、实验室检查、心电图。随访将在第35天和第65天进行，届时将进行生命体征、实验室检查、心电图和口渴量表。由于所有地点的进度缓慢，本项目已被主办方终止。