Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease (ALERT)

Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease (ALERT)

Brief Summary:
This is a Phase 3, open-label, repeat-dose study designed to assess liver safety, non-liver safety, and efficacy in subjects who previously experienced liver chemistry test abnormalities while treated with tolvaptan and were permanently discontinued from the drug for that reason. Up to 50 eligible subjects will be enrolled and treated with lixivaptan for 52 weeks following titration to an optimal dose.

Detailed Description:
This is a Phase 3, open-label, repeat-dose study designed to assess liver safety, non-liver safety, and efficacy in subjects who previously experienced liver chemistry test abnormalities while treated with tolvaptan and were permanently discontinued from the drug for that reason. Up to 50 subjects will be enrolled. Evaluations will include frequent testing of liver chemistry (every week during the Baseline and Titration Periods and every 4 weeks during the Maintenance Period), physical examinations, vital signs, safety labs (serum chemistry, hematology, urinalysis), estimated glomerular filtration rate (eGFR), urine specific gravity and osmolality determinations and trough serum concentration of lixivaptan. After meeting entry criteria during a 1-3 week Screening Period that can extend up to 8 weeks for medication adjustment, subjects will enter a 3 week no study treatment Baseline Period to obtain baseline measurements followed by a 3-6 week Titration Period during which lixivaptan administered twice daily (BID) will be titrated to a dose that is tolerated and results in a reduced trough urine specific gravity (or the maximum dose level). The minimum dose to enter the Maintenance Period is 100 mg BID. Treatment will continue for up to 52 weeks (12 months) after which study drug will be held, and final assessments obtained during the Follow-up Period of 4 weeks. The total study duration will be up to approximately 73 weeks (16.8 months).


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, single treatment group
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease Who Previously Experienced Abnormal Liver Chemistry Test Results While Receiving Tolvaptan: The ALERT Study
Actual Study Start Date: September 2, 2020
Estimated Primary Completion Date: October 2022
Estimated Study Completion Date: November 2022

Arm:
- Experimental: Lixivaptan

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