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.

低钠血症的当前选择治疗方法是水限制。该疗法是有效的，但由于口渴的明显刺激，导致生活质量差。 这项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的能力。这项研究的主要目的是评估OPC-41061的固定维持剂量在研究阶段后已纠正低钠血症的患者，并评估研究的每个阶段OPC-41061的安全性。 该研究的次要目标是评估OPC-41061在低钠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是一种苯唑啉衍生物，是由Otsuka Pharmaceutical Company开发的加压素V2肾脏亚型受体的特定且选择性的非肽拮抗剂。该研究是多中心的，随机的，开放标签的，主动控制的，剂量滴定研究的研究，用于治疗在euvoLEAMEAL或高毒液状态的euvoLEAMEAT或HYPERVOLOLICANID状态下低钠血症的治疗方法。 在研究第0天至第14天的研究第14天，在研究第14天进行评估后，患者将在GCRC中住院。志愿者将向GCRC单位报告，并将在活跃组和安慰剂组之间在第0天进行随机分组，但所有患者将在第0天和第1天接受安慰剂。在第0和1天，血清钠浓度将测量。 每个受试者都将不再添加GCRC厨房的盐标准化饮食，并将严格监测和记录输出。 安慰剂/研究药物给药后的前4小时，活动将仅限于光活动。 在这4小时的时间内，患者不应走路或代表45分钟以上。 摄入量最多将限制为每天1000毫升。 将记录尿液测量和输出。滴定住院期（研究第2至<<14）：在第2-14天，受试者将获得一片研究药物或安慰剂，带有200 cc的水。从前一天晚上，在所有学习日之前的午夜开始，患者将仅从食物中禁食。 剂量后4小时在学习天2-14时，才能提供任何饭菜。 OPC-41061的最低剂量应首先给出，并将在随后的几天继续使用更高的剂量继续。 每天将进行钠测量，生命体征，实验室测试和ECG。 流体摄入和输出监测将严格维护。门诊阶段（研究天<15至28）和随访阶段（研究日35和65）：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，将进行每隔一天，生命体征，温度和体重，实验室测试和ECG。 将在第35天和第65天进行随访，将进行生命体征，实验室测试，ECG和口渴量表。由于所有地点的审计缓慢，因此该预计已由赞助商终止。