PA-ADPKD-304: A Phase 3, Open-label, Roll-over Study to Assess Long-term Safety of Lixivaptan in Participants With Autosomal Dominant Polycystic Kidney Disease Who Completed Study PA-ADPKD-303: The ALERT Study
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
研究概览
简要总结
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan, were permanently discontinued from the drug for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
详细描述
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan that resulted in permanent discontinuation of tolvaptan for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
Assessments completed during the final 4 visits of PA-ADPKD-303, the lead-in study, will serve as the screening and baseline assessments for this roll-over study. Evaluation of eligibility will be completed at Visit 1 of this study, following signing of informed consent. Participants satisfying all study entry criteria at Visit 1 will be considered enrolled following completion of all Visit 1 study procedures and will be dispensed lixivaptan treatment to start the Lixivaptan Re-titration Period (1 to 2 weeks). During the Lixivaptan Re-titration Period, participants will have their dose of lixivaptan re-established based on the dose they were receiving at the completion of the lead-in study. Participants will continue on lixivaptan treatment for up to 104 weeks during the Maintenance Treatment Period and will be assessed at a study visit every 12 weeks. In between the quarterly study visits, participants will be required to have blood drawn for liver chemistry determinations every 4 weeks. At the end of 104 weeks, lixivaptan treatment will be stopped, and participants will enter a 4-week Follow-up Period during which final assessments of safety and efficacy will be obtained over 3 visits during a 28-day period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants with ADPKD who completed study PA-ADPKD-303
- •Continued control of hypertension without the use of a diuretic
- •Continued adherence to prohibitions on concomitant medications stated in the study PA-ADPKD-303 protocol
- •Willing to practice acceptable methods of birth control (both males who have partners of child-bearing potential and females of childbearing potential).
- •Able to provide informed consent.
排除标准
- •Any contraindication to continued treatment with lixivaptan
- •Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia)
- •New York Heart Association Functional Class 3 or 4 heart failure or other significant cardiac or electrocardiogram (ECG) findings that could pose a safety risk to the participant
- •Hypovolemia on physical examination at Screening
- •The following laboratory results based on serum drawn at Visit 24 of PA-ADPKD-303:
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >1.5 × ULN
- •Total bilirubin values >1.5 × ULN
- •eGFR <20 mL/min/1.73 m^2 based on laboratory results from Visit 26 of PA-ADPKD-303
- •A finding at Screening that precludes safe participation in the study or participants who are likely to be non-compliant with study procedures in the opinion of the Investigator or medical monitor
研究组 & 干预措施
Lixivaptan
Lixivaptan capsules 100-200mg twice daily
干预措施: Lixivaptan (Drug)
结局指标
主要结局
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
时间窗: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of participants who develop serum alanine aminotransferase (ALT) levels \>3 × the upper limit of normal (ULN) which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and resulted in discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.
次要结局
- Number of Participants Who Develop Serum ALT Levels >5 x ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment(120 days (from Screening to the end of the Maintenance Treatment Period))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(140 days (from Screening to the end of the Follow-up Period))
- Number of Participants With Potentially Clinically Important Vital Signs Findings(140 days (from Screening to the end of the Follow-up Period))
- Number of Participants Who Develop Serum ALT Values >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Dose Reduction of Lixivaptan Treatment(120 days (from Screening to the end of the Maintenance Treatment Period))
- Number of Participants With Potentially Clinically Important Clinical Laboratory Findings(140 days (from Screening to the end of the Follow-up Period))
- Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings(140 days (from Screening to the end of the Follow-up Period))
- Annualized Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Final Assessment(140 days (from Screening to the end of the Follow-up Period))