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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04064346




Registration number
NCT04064346
Ethics application status
Date submitted
19/08/2019
Date registered
21/08/2019

Titles & IDs
Public title
Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
Scientific title
A 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: The ACTION Study
Secondary ID [1] 0 0
PA-ADPKD-301
Universal Trial Number (UTN)
Trial acronym
ACTION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney 0 0
ADPKD 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lixivaptan
Treatment: Drugs - Placebo

Experimental: Lixivaptan - Lixivaptan capsules, 100-200 mg twice a day (BID)

Placebo comparator: Placebo - Matching placebo capsules BID


Treatment: Drugs: Lixivaptan
Oral vasopressin V2 receptor antagonist

Treatment: Drugs: Placebo
Matching placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Change in Estimated Glomerular Filtration Rate (eGFR) - Part 1
Timepoint [1] 0 0
Baseline to the end of Follow-up Period I (up to 71 weeks)
Primary outcome [2] 0 0
Annualized Change in Estimated Glomerular Filtration Rate (eGFR) - Part 2
Timepoint [2] 0 0
Baseline to the end of Follow-up Period II (up to 64 weeks)
Secondary outcome [1] 0 0
Number of Participants With Serum Alanine Aminotransferase (ALT) Levels >3 × the Upper Limit of Normal (ULN) - Part 1
Timepoint [1] 0 0
From the end of the Single-blind Lixivaptan Titration Period to the end of Follow-up Period I (maximum of 102 days)
Secondary outcome [2] 0 0
Number of Participants With Serum ALT Levels >3 × the ULN - Part 2
Timepoint [2] 0 0
Duration of the Lixivaptan Re-titration Period and the Maintenance Treatment Period (56 weeks) and Follow-up Period II (4 weeks)
Secondary outcome [3] 0 0
eGFR Slope - Part 1
Timepoint [3] 0 0
Baseline to the end of Double-blind Randomized Treatment Period (up to 67 weeks), with changes from baseline calculated every 4 weeks during the Double-blind Randomized Treatment Period
Secondary outcome [4] 0 0
eGFR Slope - Part 2
Timepoint [4] 0 0
Baseline to the end of the Maintenance Treatment Period (up to 60 weeks), with changes from baseline calculated every 4 weeks during the Maintenance Treatment Period
Secondary outcome [5] 0 0
Height-adjusted Total Kidney Volume (htTKV) - Part 1
Timepoint [5] 0 0
Baseline to the end of Follow-up Period I (up to 71 weeks)
Secondary outcome [6] 0 0
Height-adjusted Total Kidney Volume (htTKV) - Part 2
Timepoint [6] 0 0
Baseline to the end of Follow-up Period II (up to 60 weeks)
Secondary outcome [7] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Lixivaptan Titration Period in Part 1
Timepoint [7] 0 0
Up to 6 weeks
Secondary outcome [8] 0 0
Number of Participants With TEAEs After Randomization in Part 1
Timepoint [8] 0 0
From Randomization to study completion (up to 102 days)
Secondary outcome [9] 0 0
Number of Participants With TEAEs in Part 2
Timepoint [9] 0 0
Up to 60 weeks
Secondary outcome [10] 0 0
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings During the Lixivaptan Titration Period in Part 1
Timepoint [10] 0 0
Up to 6 weeks
Secondary outcome [11] 0 0
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings After Randomization in Part 1
Timepoint [11] 0 0
From Randomization to last clinical laboratory evaluation (up to 102 days)
Secondary outcome [12] 0 0
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings in Part 2
Timepoint [12] 0 0
Up to 60 weeks
Secondary outcome [13] 0 0
Number of Participants With Potentially Clinically Important Vital Signs Findings During the Lixivaptan Titration Period in Part 1
Timepoint [13] 0 0
Up to 6 weeks
Secondary outcome [14] 0 0
Number of Participants With Potentially Clinically Important Vital Signs Findings After Randomization in Part 1
Timepoint [14] 0 0
From Randomization to last measurement of vital signs (up to 102 days)
Secondary outcome [15] 0 0
Number of Participants With Potentially Clinically Important Vital Signs Findings in Part 2
Timepoint [15] 0 0
Up to 60 weeks
Secondary outcome [16] 0 0
Number of Participants With Potentially Clinically Significant 12-lead Electrocardiogram (ECG) Findings During the Lixivaptan Titration Period in Part 1
Timepoint [16] 0 0
Up to 6 weeks
Secondary outcome [17] 0 0
Number of Participants With Potentially Clinically Significant 12-lead ECG Findings After Randomization in Part 1
Timepoint [17] 0 0
From Randomization to last ECG (up to 102 days)
Secondary outcome [18] 0 0
Number of Participants With Potentially Clinically Significant 12-lead ECG Findings in Part 2
Timepoint [18] 0 0
Up to 60 weeks

Eligibility
Key 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 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.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/08/2022
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Renal Research - Gosford - Gosford
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Rhode Island
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Pleven
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Varna
Country [18] 0 0
Hungary
State/province [18] 0 0
Baja
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Hungary
State/province [20] 0 0
Debrecen
Country [21] 0 0
Hungary
State/province [21] 0 0
Gyöngyös
Country [22] 0 0
Hungary
State/province [22] 0 0
Pécs
Country [23] 0 0
Poland
State/province [23] 0 0
Kraków
Country [24] 0 0
Poland
State/province [24] 0 0
Warsaw
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Turkey
State/province [27] 0 0
Ankara
Country [28] 0 0
Turkey
State/province [28] 0 0
Fatih
Country [29] 0 0
Turkey
State/province [29] 0 0
Kayseri
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Palladio Biosciences
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Centessa Pharmaceuticals plc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vicente Torres, MD, PhD
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04064346