Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease (ALERT)
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ClinicalTrials.gov Identifier: NCT04152837 |
Recruitment Status :
Recruiting
First Posted : November 5, 2019
Last Update Posted : January 29, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Polycystic Kidney Disease, Adult | Drug: Lixivaptan | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Open-label, single treatment group |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | September 2, 2020 |
Estimated Primary Completion Date : | October 2022 |
Estimated Study Completion Date : | November 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: Lixivaptan
Lixivaptan oral capsules, 100-200 mg twice daily
|
Drug: Lixivaptan
Oral vasopressin V2 antagonist |
- Abnormal ALT Values [ Time Frame: 52 weeks ]Proportion of subjects who develop alanine aminotransferase (ALT) levels >3 x ULN adjudicated to be related to lixivaptan and resulted in discontinuation of the study drug
- Proportion of subjects reporting at least one adverse event [ Time Frame: 52 weeks ]Number and percent of subjects who develop at least 1 adverse event during treatment
- Abnormal Total Bilirubin Values [ Time Frame: 52 weeks ]Proportion of subjects who develop total bilirubin levels >2 x ULN during treatment with lixivaptan
- Renal Function [ Time Frame: 52 weeks ]Change from baseline in estimated glomerular filtration rate (eGFR)
- Systolic Blood Pressure (SBP) [ Time Frame: 52 weeks ]Change from baseline in SBP
- Serum Sodium Concentration [ Time Frame: 52 weeks ]Change from baseline in serum sodium concentration

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
- Baseline eGFR > 20 ml/min/1.73 m2.
- Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) at the time of Screening.
-
Documented history of:
- At least 2 elevated alanine aminotransferase (ALT) levels, 1 ALT level >2 times (x) the upper limit of normal (ULN) and 1 ALT level >3 x ULN while the subject 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
- At least 2 elevated ALT levels, 1 ALT level >2 x the subject's stable baseline level and 1 ALT level >3 x the subject's stable baseline level while the subject 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 tolvaptan 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.
- Appropriate control of hypertension including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker (unless not considered appropriate for the subject) without the use of a diuretic in concert with Kidney Disease: Improving Global Outcomes (KDIGO) "Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease".
Exclusion Criteria:
- Known sensitivity or idiosyncratic reaction to any compound present in lixivaptan and related compounds.
- Hypovolemia or inability to perceive thirst
- 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.
- Prior use of tolvaptan within the past 3 months or until a previously elevated ALT level has returned to ≤1 x ULN.
- 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 3 months
- 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, transplanted 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.
- Clinically significant liver disease or impairment or active chronic hepatitis at Screening.
- Elevated baseline levels of serum ALT or total bilirubin.
- History of drug or alcohol abuse in the past 2 years.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04152837
Contact: Neil Shusterman, MD | 267-609-7553 | ClinicalTrials@palladiobio.com | |
Contact: Robin Waymer | 267-609-7553 | ClinicalTrials@palladiobio.com |
United States, Alabama | |
University of Alabama Birmingham | Not yet recruiting |
Birmingham, Alabama, United States, 35233 | |
Contact: Amy Bottomlee amybottomlee@uabmc.edu | |
Principal Investigator: Michal Mrug, Md | |
United States, California | |
University of California Los Angeles | Not yet recruiting |
Los Angeles, California, United States, 90025 | |
Contact: XiaoXiao Yin XiaoxiaoYin@mednet.ucla.edu | |
Principal Investigator: Anjay Rastogi, MD, PhD | |
United States, Illinois | |
University of Chicago Medicine & Biological Sciences | Recruiting |
Chicago, Illinois, United States, 60637 | |
Contact: Serdar Aydin, MD serdarmd@medicine.bsd.uchicago.edu | |
Principal Investigator: Arlene Chapman, MD | |
United States, Maryland | |
University of Maryland School of Medicine | Recruiting |
Baltimore, Maryland, United States, 21201 | |
Contact: Charalett Diggs charalett.diggs@som.umaryland.edu | |
Principal Investigator: Stephen Seliger, MD | |
United States, Michigan | |
St. Clair Nephrology | Recruiting |
Roseville, Michigan, United States, 48066 | |
Contact: Rosemarie Henschel 313-432-6273 RHenschel@scsp.net | |
Principal Investigator: Marjana Dimitrijevic, MD | |
United States, Minnesota | |
Mayo Clinic | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Contact: Kathleen Leistikow leistikow.kathleen@mayo.edu | |
Principal Investigator: Vicente Torres, MD, PhD | |
United States, North Carolina | |
Brookview Hills Research Associates, LLC | Recruiting |
Winston-Salem, North Carolina, United States, 27103 | |
Contact: Cindy Vanhoy 336-245-6320 CVanhoy@brookviewhills.com | |
Principal Investigator: Gregory Greenwood, MD | |
United States, Pennsylvania | |
Northeast Clinical Research Center, LLC | Recruiting |
Bethlehem, Pennsylvania, United States, 18107 | |
Contact: Stephanie Hanzl steph.hanzl@necresearch.org | |
Principal Investigator: Nelson Kopyt, DO | |
United States, Virginia | |
Nephrology Associates of Northern Virginia, Inc. | Recruiting |
Fairfax, Virginia, United States, 22033 | |
Contact: Musirah Khan 703-961-0565 ext 224 musirah.khan@nanvonline.com | |
Principal Investigator: Amadshah Mirkhel, MD |
Responsible Party: | Palladio Biosciences |
ClinicalTrials.gov Identifier: | NCT04152837 |
Other Study ID Numbers: |
PA-ADPKD-303 |
First Posted: | November 5, 2019 Key Record Dates |
Last Update Posted: | January 29, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Kidney Diseases Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urologic Diseases Kidney Diseases, Cystic |
Abnormalities, Multiple Congenital Abnormalities Ciliopathies Genetic Diseases, Inborn |