Loading clinical trials...

Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease | Clinical Trials | Clareo Health

TERMINATEDPHASE3

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

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

NCT04152837•Palladio Biosciences

View on ClinicalTrials.gov

Summary

Detailed Description

This is a Phase 3, open-label, repeat-dose study designed to assess liver safety, non-liver safety, and efficacy of lixivaptan in participants who previously experienced liver chemistry test abnormalities while treated with tolvaptan and were permanently discontinued from the drug for that reason. Up to 50 participants will be enrolled and treated. 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- to 3-week Screening Period that can extend up to 8 weeks for medication adjustment, participants will enter a 3-week no study treatment Baseline Period to obtain baseline measurements followed by a 3- to 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 to 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).

Eligibility

Age

18 - 65 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Male or female, between 18 and 65 years of age (inclusive) at the time of Screening.
•Documented diagnosis of ADPKD by imaging or genetic analysis previously treated with tolvaptan for that indication.
•Screening eGFR ≥ 20 mL/min/1.73 m\^2.
•Body mass index (BMI) between 18 and 35 kg/m\^2 (inclusive) at the time of Screening.
•Documented history of:
•* Based on upper limit of normal (ULN): At least 2 elevated alanine aminotransferase (ALT) levels; 1 ALT level \>2 x ULN and 1 ALT level \>3 x ULN while the participant was receiving tolvaptan, or within 4 weeks after tolvaptan discontinuation, with no other explanation for the ALT elevations. The 2 elevated ALT measurements could be recorded during the same instance of liver injury or during distinct instances; OR
•* Based on the participant's stable baseline as determined by the Investigator: At least 2 elevated ALT levels; 1 ALT level \>2 x the participant's stable baseline level and 1 ALT level \>3 x the participant's stable baseline level while the participant was receiving tolvaptan, or within 4 weeks after tolvaptan discontinuation, with no other explanation for the ALT elevations; provided that at least one ALT elevation was \>2 x ULN. The 2 elevated ALT measurements could be recorded during the same instance of liver injury or during distinct instances; OR
•* A pattern of ALT elevations deemed by the Investigator to be consistent with tolvaptan liver injury with no other explanation for the ALT elevations and agreement of the medical monitor and sponsor.
•Permanent discontinuation of prior tolvaptan treatment because of the ALT abnormality.
•If re-challenge with tolvaptan was performed, the ALT level must have increased to \>2 x ULN upon rechallenge or the ALT level was increasing but tolvaptan was stopped for patient safety reasons before it reached \> 2 x ULN after having previously normalized.
+3 more criteria

Exclusion Criteria

•Known sensitivity or idiosyncratic reaction to any compound present in lixivaptan and related compounds.
•Hypovolemia at Screening.
•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, Seville oranges, or St. John's wort.
•Simvastatin at total daily doses \>10 mg or amlodipine at total daily doses \>5 mg.
•Use of tolvaptan within the 3 months prior to Screening or until a previously elevated ALT level has returned to ≤1 x ULN for at least 3 months.
•Use of lixivaptan or participation in a clinical study with lixivaptan within the 3 months prior to Screening.
•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 3 months prior to Screening.
•Requirement for chronic diuretic use.
+11 more criteria

Locations (6)

University of California Los Angeles

Los Angeles, California, United States

University of Chicago Medicine & Biological Sciences

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Brookview Hills Research Associates, LLC

Winston-Salem, North Carolina, United States

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, United States

Nephrology Associates of Northern Virginia, Inc.

Fairfax, Virginia, United States

Key Dates

Start Date

September 2, 2020

Primary Completion Date

July 29, 2022

Completion Date

July 29, 2022

Last Updated

April 10, 2023

Enrollment

ACTUAL participants

Conditions

Polycystic Kidney Disease, AdultADPKD

Interventions

Lixivaptan

DRUG

Metabolic Impacts of Ren-Nu: A Dietary Program for Polycystic Kidney Disease

NCT07454174

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

View study

RECRUITING

Autosomal Dominant Polycystic Kidney Disease (ADPKD) Study

NCT04338048

ADPKD

View study

RECRUITING

Genetics in the Progression of Nephropathies

NCT06416761

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 10, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Metabolic Impacts of Ren-Nu: A Dietary Program for Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) Study

Genetics in the Progression of Nephropathies

A Possible Founding PKD2 Mutation Associated With Variable Phenotypes of ADPKD in Bergamo Province

Study of Tamibarotene in Patients With ADPKD

Bempedoic Acid Therapy for Polycystic Kidney Disease