SR121463B IN PATIENTS W/ SYNDROME INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

SR121463B 用于抗利尿激素分泌不当综合征患者

• 批准号: 7608484
• 负责人: JOSEPH G VERBALIS
• 金额: $ 1.49万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608484
• 关键词: Clinical; Computer Retrieval of Information on Scientific Projects Database; Daily; Dose; Evaluation; Funding; Grant; Hospitalization; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Institution; Instruction; Intake; Laboratories; Liquid substance; Monitor; Normal Range; Numbers; Pallister syndrome 1; Patients; Pharmaceutical Preparations; Rate; Recruitment Activity; Refractory; Research; Research Personnel; Resources; Safety; Schedule; Serum; Sodium; Source; Titrations; United States National Institutes of Health; Visit; Water consumption; base; day; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To assess the long-term safety and tolerability SR121463B in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) This is a multicenter worldwide study. A minimum of 55 patients will be recruited to insure 45 patients with 6 months exposure. This number of patients may be revised in case of necessity. The eligible patients will receive four available daily doses of SR121463B (5 or 12.5 or 25 or 50 mg) based on their response for up to 343 days while they are under regular monitoring of laboratory and clinical parameters. The treatment aims to obtain a serum sodium within a normal range (135-145 mmol/L). The rate of correction of serum sodium should not exceed 8 mmoI/L/day over the first 2 days in order to avoid myelinolysis while correcting hyponatremia. In case of rapid correction of serum sodium, the Investigator should increase the fluid intake accordingly and perform additional assessment of serum sodium during the afternoon or evening if necessary (see Section 10.5 Safety instruction). The dose-adjustment will be according to the following rules. For the initial dose on Day 1, patients should be given 25 mg/day of SR121463B. From Day 2 to the end of the study, based on the new results of serum sodium, the Investigator will adjust at each visit the daily dose of SR121463B (decrease to 12.5 or 5 mg, discontinuation of the medication, increase to 50 mg, or no change) and/or the daily fluid intake. For patients with hyponatremia refractory to 50 mg/day of SR121463B for at least 28 days, the Investigator may consider to increase the dose after contacting the Trial Monitor. On Day 56, all patients with serum sodium > 135 mmol/L on the day of the visit who are still on study medication will discontinue the medication and have regular monitoring of laboratory and clinical parameters until the end of the study. Patients who re-develop hyponatremia (serum sodium < 135 mmol/L) on two consecutive visits, will re-start the medication with their last dose (see the proposed Study Flow Chart). Additional Visits for serum sodium assessment are permitted if necessary in order to adjust the treatment for reaching and maintaining normonatremia. Any effort should be made by the Investigator to find the minimum efficacious dose using down titration. If hypernatremia (serum sodium > 145 mmol/L) develops during the study, the drug should be temporarily discontinued and the patient should receive appropriate water intake. Patients who have a serum sodium > 135 mmol/L on two consecutive visits, 28 days apart after drug discontinuation, are considered "cured". These patients will discontinue the study and perform the evaluations scheduled for the last visit of the study (End of Study Visit). Hospitalization is not mandatory and its relevance is at the discretion of the Investigator. However, hospitalization is recommended (mainly for practical reasons of monitoring) from Day -1 to Day 3 (morning) in all patients.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 评估长期安全性和耐受性 SR 121463 B在抗利尿激素分泌不当综合征（SIADH）患者中的应用 这是一项多中心全球研究。将招募至少55例患者，以确保45例患者暴露6个月。如有必要，可修改这一患者人数。合格患者将根据其应答接受4次可用的SR 121463 B每日剂量（5或12.5或25或50 mg），最长持续343天，同时定期监测实验室和临床参数。 治疗的目的是使血清钠在正常范围内（135-145 mmol/L）。在前2天内，血清钠的校正率不应超过8 mmoI/L/天，以避免在校正低钠血症时发生髓鞘溶解。如果血清钠快速校正，研究者应相应增加液体摄入量，并在必要时在下午或晚上进行额外的血清钠评估（见第10.5节安全性说明）。 剂量调整将根据以下规则进行。对于第1天的初始剂量，患者应接受25 mg/天的SR 121463 B。从第2天至研究结束，根据血清钠的新结果，研究者将在每次访视时调整SR 121463 B的日剂量（降低至12.5或5 mg、停药、增加至50 mg或不变）和/或每日液体摄入量。对于50 mg/天SR 121463 B治疗至少28天无效的低钠血症患者，研究者可在联系试验监查员后考虑增加剂量。 在第56天，在访视当天血清钠> 135 mmol/L且仍在服用研究药物的所有患者将停止药物治疗，并定期监测实验室和临床参数，直至研究结束。在连续两次访视中再次发生低钠血症（血清钠< 135 mmol/L）的患者将重新开始末次给药（见拟定的研究流程图）。 如有必要，允许进行额外的血清钠评估访视，以调整治疗以达到和维持正常钠血症。研究者应尽一切努力使用剂量下调找到最小有效剂量。 如果在研究期间发生高钠血症（血清钠> 145 mmol/L），应暂时停用药物，患者应摄入适当的水。 在停药后相隔28天的连续两次访视中血清钠> 135 mmol/L的患者被视为“治愈”。这些患者将中止研究，并在研究末次访视（研究结束访视）时进行计划的评价。 住院不是强制性的，其相关性由研究者决定。但是，建议所有患者从第-1天至第3天（早晨）住院（主要是出于监测的实际原因）。