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

• Status: Recruiting
• Trial end date: 2026-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Palladio Biosciences

Criteria

Inclusion Criteria:

• Diagnosis of ADPKD by appropriate imaging or genetic testing

• Mayo Clinic MRI imaging classification of 1C, 1D or 1E

• eGFR ≥25 mL/min/1.73 m2 and ≤90 mL/min/1.73 m2

• Body mass index (BMI) between 18 and 40 kg/m2

• Control of hypertension consistent with KDIGO guidelines without a diuretic

• Willing to practice acceptable methods of birth control (both males who have partners of child-bearing potential and females of childbearing potential)

Exclusion Criteria:

• Known sensitivity or idiosyncratic reaction to any compound present in lixivaptan and related compounds.

• Hypovolemia or inability to perceive thirst

• Abnormal serum sodium concentration at Screening

• Subjects who have taken any investigational drug or used an investigational device within 30 days, or 5 half-lives, whichever is longer, prior to Screening

• Subjects who are taking, have taken within the past 2 weeks, or are expected to be taking, strong or moderate CYP3A4 or CYP2C8 inhibitors or inducers including regular use of grapefruit juice or Seville oranges

• Prior use of tolvaptan or lixivaptan within the past 2 months.

• Prior use of conivaptan, somatostatin analogs (e.g. lanreotide, pasireotide, octreotide, etc.), metformin, nicotinamide, bardoxolone, venglustat, demeclocycline, or mammalian target of rapamycin (mTOR) kinase inhibitors (e.g. everolimus, sirolimus, etc.) to treat ADPKD within the past 2 months

• Prior use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, empagliflozin, etc.) within the past 2 months or expected need for initiation of treatment with a SGLT2 inhibitor during the study.

• Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor within the past 2 months or expected need for initiation of treatment with a HIF-PH inhibitor during the study.

• Requirement for chronic diuretic use

• Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant renal disease, renal cancer, transplanted kidney, single kidney, recent kidney surgery within the past 6 months (including cyst drainage or fenestration) or acute kidney injury within past 6 months

• 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 subject.

• Positive test results for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV).

• History of infection with human immunodeficiency virus (HIV) unless the participant is stable and doing well on a non-CYP interacting anti-retroviral therapy (ART) regimen and who has not required more than 2 changes in their ART regimen since treatment inception.

• History of clinically significant drug or alcohol abuse in the past 2 years.

• Contraindication to or interference with MRI assessments.

• Malignancy within the past 5 years except for those not considered to affect participant survival.