ACTION Study Initiation
Recruitment has commenced in the global Phase 3 ACTION Study which consists of a two-arm, double-blind, placebo-controlled, randomized phase (Part 1) followed by a single-arm, open-label phase
ACTION Study Initiation
Recruitment has commenced in the global Phase 3 ACTION Study which consists of a two-arm, double-blind, placebo-controlled, randomized phase (Part 1) followed by a single-arm, open-label phase (Part 2). The study will evaluate the benefit and safety of lixivaptan that has been titrated to a maximum tolerated dose between 100-200 mg BID in subjects with ADPKD and a Mayo Clinic MRI imaging classification of 1C, 1D or 1E and an estimated glomerular filtration rate (eGFR) ≥25 and ≤90 mL/min/1.73 m2.
The primary analysis of the ACTION Study will be performed at the end of Part 1 of the trial, which will have a 2:1 randomization (lixivaptan:placebo) and is designed to assess lixivaptan in slowing the decline in renal function as measured at 52 weeks by the difference in eGFR between the lixivaptan-treated and placebo-treated subjects. Final efficacy measurements at the end of the double-blind period will be conducted while the subject is off study drug over three successive clinic visits. The sample size of the study will be up to 1,350 subjects to provide 90% power to the primary analysis, aiming to detect a 1.4 mL/min/1.73 m2 eGFR difference between lixivaptan-treated and placebo-treated subjects. Thirteen clinical sites have been initiated and the trial is ultimately expected to enroll subjects across more than 200 sites in more than 20 countries. As previously disclosed, the Company expects to dose the first subject in the ACTION Study by the first quarter of 2022.
All subjects successfully completing Part 1 are expected to continue into Part 2 of the study and will be treated with lixivaptan for an additional 54-56 weeks to further assess the sustainability of the potential benefit on eGFR change over a two-year period. Consistent with Part 1, updated efficacy measurements will be conducted off study drug. Both parts of the study will contribute to further establishing the safety profile of lixivaptan. An independent data monitoring committee will periodically review all safety data including the liver chemistry data for all subjects throughout the study. The Company anticipates completing enrollment in 2H 2023 and, pending positive data, plans to submit a New Drug Application (NDA) after completion of the one-year double-blind portion of the study (Part 1).