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

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Autosomal Dominant Polycystic Kidney, ADPKD

In brief

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 kidney 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.

Key facts

Study ID

NCT04064346

Run by

Palladio Biosciences

People needed

12

Starts

2021-10-28

Expected to finish

2022-08-03

Last updated by the study team

2023-02-06

Who can join

Age: 18 and older, up to 60. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 m\^2.
• Body mass index between 18 and 40 kg/m\^2.
• Control of hypertension consistent with the 2021 Kidney Disease: Improving Global Outcomes guidelines without a diuretic and with an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) unless not considered medically appropriate.
• 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.

You may not qualify if…

• Known sensitivity or idiosyncratic reaction to lixivaptan and/or its excipients.
• Hypovolemia.
• 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, demeclocycline, or mammalian target of rapamycin kinase inhibitors (e.g., everolimus, sirolimus, etc.), or KetoCitra™ or any beta-hydroxybutyrate containing supplements 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 ongoing diuretic use.
• Advanced diabetes (e.g., glycosylated hemoglobin >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant kidney disease, kidney 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 ECG findings that could pose a safety risk to the subject.
• Positive test results for hepatitis B surface antigen or hepatitis C antibody.
• History of infection with human immunodeficiency virus unless the participant is clinically 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.
• Contraindications to or interference with MRI assessments.
• Malignancy within the past 5 years except for those not considered to affect participant survival.
• Medical history or findings that preclude safe participation in the trial or participants who are likely to be non-compliant with trial procedures in the opinion of the Investigator or medical monitor.
• Clinically significant liver disease or impairment or alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin values >1.2 x ULN during Screening. Note: This criterion will preliminarily be reviewed at Visit 2 based on Visit 1a and Visit 1b results (if Visit 1b is required). The criterion must be re-evaluated no later than Visit 3 when results for Visit 2 are available.
• Simvastatin at a total daily dose >10 mg or amlodipine at a total daily dose >5 mg.

Where it is running

• Nephrology Associates, PC - Greystone — Hoover, Alabama, United States
• Nephrology Consultants, LLC — Huntsville, Alabama, United States
• Arizona Kidney Disease & Hypertension Center - Scottsdale / Pima — Scottsdale, Arizona, United States
• JEM Research Institute — Atlantis, Florida, United States
• Elixia at Florida Kidney Physicians - Southeast — Fort Lauderdale, Florida, United States
• Qway Research — Hialeah, Florida, United States
• South Florida Nephrology Associates PA — Lauderdale Lakes, Florida, United States
• Total Research Group, LLC — Miami, Florida, United States
• Innovation Medical Research Center, Inc — Palmetto Bay, Florida, United States
• Florida Kidney Physicians - Tampa — Tampa, Florida, United States
• Clinical Site Partners, LLC — Winter Park, Florida, United States
• Tufts Medical Center, Inc, — Boston, Massachusetts, United States
• St Clair Nephrology Research, LLC — Roseville, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Clinical Research Consultants, LLC — Kansas City, Missouri, United States
• Angel City Research, Inc — Morrisville, North Carolina, United States
• Northeast Clinical Research Center, LLC — Bethlehem, Pennsylvania, United States
• Brown Medicine - Brown Physicians Patient Center — Riverside, Rhode Island, United States
• Knoxville Kidney Center LLC — Knoxville, Tennessee, United States
• Prolato Clinical Research Center (PCRC) — Houston, Texas, United States
• Clinical Advancement Center, PLLC — San Antonio, Texas, United States
• Utah Kidney Research Institute — Salt Lake City, Utah, United States
• Nephrology Associates of Northern Virginia, Inc — Fairfax, Virginia, United States
• Renal Research - Gosford — Gosford, New South Wales, Australia
• University Multiprofile Hospital for Active Treatment — Pleven, Bulgaria

Full record on ClinicalTrials.gov

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