Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ACTION)

Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ACTION)

Brief Summary:
This is a Phase 3 trial consisting of a 2-arm, double-blind, placebo-controlled, randomized phase (Part 1) followed by a single-arm open-label phase (Part 2) to demonstrate the efficacy and safety of lixivaptan in participants with autosomal dominant polycystic kidney disease (ADPKD). Part 1 of the trial is designed to demonstrate the efficacy of lixivaptan in slowing the decline in renal function as measured by the difference in estimated glomerular filtration rate (eGFR) between the lixivaptan-treated and placebo-treated participants. Part 2 of the study is designed to provide confirmation of the durability of this effect. Additionally, both parts of the study will contribute to understanding the safety of lixivaptan, particularly any effects on liver chemistry tests.

Detailed Description:
Part 1: Approximately 2000 participants with ADPKD will be screened in order to qualify the 1200 individuals who will then be randomized to receive lixivaptan or placebo. Each participant has a 2/3 chance of receiving lixivaptan and a 1/3 chance of receiving placebo. After meeting entry criteria during screening, participants will begin receiving treatment with study drug. At some point during Part 1, all participants will receive placebo and all participants will receive lixivaptan. The dose will be adjusted to the highest level that is tolerated and that dose will be continued for the rest of Part 1. Similarly, at some point participants will be randomized to lixivaptan or placebo. Throughout Part 1 the study drug will look identical regardless of whether it is placebo or lixivaptan. After 58-59 weeks, the administration of study drug will be paused, and final eGFR assessments for Part 1 will be obtained during 3 follow-up visits starting over a period of 28 days.

Part 2: All participants entering Part 1 will continue into Part 2 of the study and be treated with the active drug, lixivaptan, for an additional 54-56 weeks unless study drug was previously discontinued for a safety reason or a participant withdraws consent. At the end of that time, study drug will be discontinued, and final eGFR assessments for Part 2 will be obtained during 3 follow-up visits starting over a period of 28 days.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, randomized, placebo-controlled in Part 1 Single-arm, active drug in Part 2
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Sponsor - identical appearing active and placebo capsules in Part 1; all active capsules in Part 2
Primary Purpose: Treatment
Official Title: A 2-Year, Phase 3 Study of the Efficacy and Safety of Lixivaptan in Participants With Autosomal Dominant Polycystic Kidney Disease Consisting of a 1-year Double-blind, Placebo-controlled, Randomized Phase and a 1-year Open-label Phase
Actual Study Start Date: October 28, 2021
Estimated Primary Completion Date: February 2025
Estimated Study Completion Date: April 2026

Arm:
- Experimental: Lixivaptan - Part 1 and Part 2
- Placebo Comparator: Placebo - Part 1

View full details