Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ACTION)
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ClinicalTrials.gov Identifier: NCT04064346 |
Recruitment Status :
Recruiting
First Posted : August 21, 2019
Last Update Posted : May 17, 2022
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Condition or disease | Intervention/treatment | Phase |
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Autosomal Dominant Polycystic Kidney ADPKD | Drug: Lixivaptan Drug: Placebo | Phase 3 |
Part 1: Approximately 2500 participants with ADPKD will be screened in order to qualify the 1350 individuals who will then be randomized to receive lixivaptan or placebo. Each participant has a 2/3 chance of receiving lixivaptan and a 1/3 chance of receiving placebo. After meeting entry criteria during screening, participants will begin receiving treatment with study drug. At some point during Part 1, all participants will receive placebo and all participants will receive lixivaptan. The dose will be adjusted to the highest level that is tolerated and that dose will be continued for the rest of Part 1. Similarly, at some point participants will be randomized to lixivaptan or placebo. Throughout Part 1 the study drug will look identical regardless of whether it is placebo or lixivaptan. After 58-59 weeks, the administration of study drug will be paused, and final eGFR assessments for Part 1 will be obtained during 3 follow-up visits starting over a period of 28 days.
Part 2: All participants entering Part 1 will continue into Part 2 of the study and be treated with the active drug, lixivaptan, for an additional 54-56 weeks unless study drug was previously discontinued for a safety reason or a participant withdraws consent. At the end of that time, study drug will be discontinued, and final eGFR assessments for Part 2 will be obtained during 3 follow-up visits starting over a period of 28 days.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 1350 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Double-blind, randomized, placebo-controlled in Part 1 Single-arm, active drug in Part 2 |
Masking: | Triple (Participant, Care Provider, Investigator) |
Masking Description: | Sponsor - identical appearing active and placebo capsules in Part 1; all active capsules in Part 2 |
Primary Purpose: | Treatment |
Official Title: | A 2-Year, Phase 3 Study of the Efficacy and Safety of Lixivaptan in Participants With Autosomal Dominant Polycystic Kidney Disease Consisting of a 1-year Double-blind, Placebo-controlled, Randomized Phase and a 1-year Open-label Phase |
Actual Study Start Date : | October 28, 2021 |
Estimated Primary Completion Date : | February 2025 |
Estimated Study Completion Date : | April 2026 |

Arm | Intervention/treatment |
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Experimental: Lixivaptan - Part 1 and Part 2
Lixivaptan capsules, 100-200 mg twice a day (BID)
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Drug: Lixivaptan
Oral vasopressin 2 receptor antagonist |
Placebo Comparator: Placebo - Part 1
Matching placebo capsules BID
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Drug: Placebo
Matching placebo |
- Estimated Glomerular Filtration Rate (eGFR) - Part 1 [ Time Frame: 52 weeks ]Annualized change in eGFR from baseline to follow-up in Part 1
- Serum alanine aminotransferase (ALT) levels [ Time Frame: 52 weeks ]Incidence of serum ALT levels >3 x ULN in participants randomized to lixivaptan compared to those randomized to placebo in Part 1
- Estimated Glomerular Filtration Rate (eGFR) - Part 2 [ Time Frame: 52 weeks ]Annualized change in eGFR from baseline to follow-up in Part 2
- eGFR Slope in Part 1 [ Time Frame: 52 weeks ]Annualized rate of change (slope) in eGFR, based on all eGFR determinations during the Double-Blind, Randomized Treatment Period in Part 1
- Total Kidney Volume (TKV) [ Time Frame: 52 weeks ]Annualized rate of change from baseline to follow-up in TKV, determined by MRI, in Part 1
- Non-hepatic safety in Part 1 [ Time Frame: 52 weeks ]Incidence of adverse events by treatment group in Part 1
- Non-hepatic safety in Part 2 [ Time Frame: 52 weeks ]Incidence of adverse events in Part 2

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

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): NCT04064346
Contact: Robin Waymer | 267-609-7553 | ClinicalTrials@palladiobio.com | |
Contact: Neil Shusterman, MD | 267-609-7553 | ClinicalTrials@palladiobio.com |

Principal Investigator: | Vicente Torres, MD, PhD | Mayo Clinic |
Responsible Party: | Palladio Biosciences |
ClinicalTrials.gov Identifier: | NCT04064346 |
Other Study ID Numbers: |
PA-ADPKD-301 |
First Posted: | August 21, 2019 Key Record Dates |
Last Update Posted: | May 17, 2022 |
Last Verified: | May 2022 |
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 |
Arthrogryposis Kidney Diseases Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urologic Diseases Joint Diseases Musculoskeletal Diseases |
Muscular Diseases Musculoskeletal Abnormalities Congenital Abnormalities Kidney Diseases, Cystic Abnormalities, Multiple Ciliopathies Genetic Diseases, Inborn |