Status:
TERMINATED
Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
Lead Sponsor:
Palladio Biosciences
Collaborating Sponsors:
Centessa Pharmaceuticals plc
Conditions:
Autosomal Dominant Polycystic Kidney
ADPKD
Eligibility:
All Genders
18-60 years
Phase:
PHASE3
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 ...
Detailed Description
Part 1: Approximately 2250 participants with ADPKD will be screened in order to qualify the 1350 individuals who will proceed through the Placebo Run-in Period, the Lixivaptan Titration Period, and th...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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.
Key Trial Info
Start Date :
October 28 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 3 2022
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT04064346
Start Date
October 28 2021
End Date
August 3 2022
Last Update
February 6 2023
Active Locations (43)
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1
Nephrology Associates, PC - Greystone
Hoover, Alabama, United States, 35242
2
Nephrology Consultants, LLC
Huntsville, Alabama, United States, 35805-4104
3
Arizona Kidney Disease & Hypertension Center - Scottsdale / Pima
Scottsdale, Arizona, United States, 85258
4
JEM Research Institute
Atlantis, Florida, United States, 33462