Polycystic Kidney Disease, AdultPhase 3NCT05208866
Roll-over Study to Assess Safety of Lixivaptan in Participants With ADPKD Who Completed Study PA-ADPKD-303
A Phase 3 study testing Lixivaptan in people with Polycystic Kidney Disease, Adult, run by Palladio Biosciences at 1 site in United States.
Trial summary
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan, were permanently discontinued from the drug for that… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycystic Kidney Disease, Adult
- What is being tested?
- Lixivaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2022to 29 Jul 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants with ADPKD who completed study PA-ADPKD-303
- Continued control of hypertension without the use of a diuretic
- Continued adherence to prohibitions on concomitant medications stated in the study PA-ADPKD-303 protocol
- 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.
Who cannot join
- Any contraindication to continued treatment with lixivaptan
- 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 participant
- Hypovolemia on physical examination at Screening
- The following laboratory results based on serum drawn at Visit 24 of PA-ADPKD-303:
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >1.5 × ULN
Show all 9Show fewer
- Total bilirubin values >1.5 × ULN
- eGFR <20 mL/min/1.73 m^2 based on laboratory results from Visit 26 of PA-ADPKD-303
- A finding at Screening that precludes safe participation in the study or participants who are likely to be non-compliant with study procedures in the opinion of the Investigator or medical monitor
Trial locations and contacts
1 site in 1 country.
United States1 site
Northeast Clinical Research Center, LLC
Bethlehem, Pennsylvania, 18107
About this study
Official title: PA-ADPKD-304: A Phase 3, Open-label, Roll-over Study to Assess Long-term Safety of Lixivaptan in Participants With Autosomal Dominant Polycystic Kidney Disease Who Completed Study PA-ADPKD-303: The ALERT Study
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan, were permanently discontinued from the drug for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
Read the detailed description
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan that resulted in permanent discontinuation of tolvaptan for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
Assessments completed during the final 4 visits of PA-ADPKD-303, the lead-in study, will serve as the screening and baseline assessments for this roll-over study. Evaluation of eligibility will be completed at Visit 1 of this study, following signing of informed consent. Participants satisfying all study entry criteria at Visit 1 will be considered enrolled following completion of all Visit 1 study procedures and will be dispensed lixivaptan treatment to start the Lixivaptan Re-titration Period (1 to 2 weeks). During the Lixivaptan Re-titration Period, participants will have their dose of lixivaptan re-established based on the dose they were receiving at the completion of the lead-in study. Participants will continue on lixivaptan treatment for up to 104 weeks during the Maintenance Treatment Period and will be assessed at a study visit every 12 weeks. In between the quarterly study visits, participants will be required to have blood drawn for liver chemistry determinations every 4 weeks. At the end of 104 weeks, lixivaptan treatment will be stopped, and participants will enter a 4-week Follow-up Period during which final assessments of safety and efficacy will be obtained over 3 visits during a 28-day period.
- Conditions
- Polycystic Kidney Disease, Adult
- Being tested
- Lixivaptan
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LixivaptanDrug
Oral vasopressin V2 receptor antagonist
| Study group | Role | What they receive |
|---|---|---|
| Lixivaptan | Experimental | Lixivaptan capsules 100-200mg twice daily Receives: Drug: Lixivaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
Number of participants who develop serum alanine aminotransferase (ALT) levels >3 × the upper limit of normal (ULN) which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and resulted in discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.
Measured: 120 days (from Screening to the end of the Maintenance Treatment Period)
Secondary outcomes (7)
Number of Participants Who Develop Serum ALT Levels >5 x ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
Number of participants who develop serum ALT levels >5 × ULN which are assessed by the independent HERC to be at least probably related to lixivaptan and resulted in discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.
Measured: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of Participants Who Develop Serum ALT Values >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Dose Reduction of Lixivaptan Treatment
Number of participants who develop serum ALT levels >3 × ULN that were assessed by the independent HERC to be at least probably related to lixivaptan and resulted in dose reduction of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.
Measured: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with TEAEs during the Lixivaptan Re-titration Period, the Maintenance Treatment Period, or the Follow-up Period.
Measured: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings
Number of participants with clinical laboratory findings (non-hepatic clinical chemistry, hematology, and urinalysis) recorded during the Lixivaptan Re-titration Period, the Maintenance Treatment Period, or the Follow-up Period, and considered to be potentially clinically important.
Measured: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important Vital Signs Findings
Number of participants with vital signs findings (heart rate, diastolic and systolic blood pressure, and weight) recorded during the Lixivaptan Re-titration Period, the Maintenance Treatment Period, or the Follow-up Period, and considered to be potentially clinically important.
Measured: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings
Number of participants with ECG findings recorded during the Lixivaptan Re-titration Period, the Maintenance Treatment Period, or the Follow-up Period, and considered to be potentially clinically important (defined as a QT interval corrected for heart rate according to Fridericia's formula [QTcF] ≥ 450 msec).
Measured: 140 days (from Screening to the end of the Follow-up Period)
Annualized Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Final Assessment
Baseline eGFR is defined as the mean of the 3 eGFR assessments obtained at Visits 25, 26 and 27 of study PA-ADPKD-303 (if any values are missing, the remaining values will be used to determine the baseline eGFR). The endpoint eGFR is defined as the mean of 3 eGFR assessments obtained during the Follow-up Period (if any values are missing, the remaining values will be used to determine the endpoint eGFR). The change in eGFR from Baseline to Final Assessment will be provided.
Measured: 140 days (from Screening to the end of the Follow-up Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start10 Feb 2022
- Primary completion29 Jun 2022
- Study completion29 Jul 2022
Why it stopped: The decision is based on a thorough reassessment of the commercial potential of lixivaptan as a potential best-in-class therapy for patients with ADPKD.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Kidney Disease, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group, open-label study
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Palladio Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Centessa Pharmaceuticals plc
- Responsible party
- Sponsor
- Investigators
- Nelson Kopyt, DO, Principal investigator, Northeast Clinical Research Center, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208866
- Sponsor's protocol ID
- PA-ADPKD-304
- Status last verified
- Apr 2023
- First submitted
- 7 Jan 2022
- Last updated
- 12 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J, Rochon J; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf. 2009;32(1):55-68. doi: 10.2165/00002018-200932010-00005.
PubMed 19132805
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PA-ADPKD-304: A Phase 3, Open-label, Roll-over Study to Assess Long-term Safety of Lixivaptan in Participants With Autosomal Dominant Polycystic Kidney Disease Who Completed Study PA-ADPKD-303: The ALERT Study
- ClinicalTrials.gov ID
- NCT05208866
- Acronym / sponsor ID
- PA-ADPKD-304
- Conditions
- Polycystic Kidney Disease, Adult
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision is based on a thorough reassessment of the commercial potential of lixivaptan as a potential best-in-class therapy for patients with ADPKD.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Palladio BiosciencesIndustry (pharma, biotech, devices)
- Collaborators
- Centessa Pharmaceuticals plc
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- 29 Jun 2022 (actual)
- Study completion
- 29 Jul 2022 (actual)
- First posted
- 26 Jan 2022 (actual)
- Results
- Posted 10 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan, were permanently discontinued from the drug for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
Detailed description
This is a Phase 3, open-label, roll-over study to demonstrate the continued hepatic and non-hepatic safety and renal efficacy of lixivaptan in participants with ADPKD who previously experienced abnormal liver chemistry test results while treated with tolvaptan that resulted in permanent discontinuation of tolvaptan for that reason, and subsequently completed study PA-ADPKD-303, the open-label lead-in study with lixivaptan.
Assessments completed during the final 4 visits of PA-ADPKD-303, the lead-in study, will serve as the screening and baseline assessments for this roll-over study. Evaluation of eligibility will be completed at Visit 1 of this study, following signing of informed consent. Participants satisfying all study entry criteria at Visit 1 will be considered enrolled following completion of all Visit 1 study procedures and will be dispensed lixivaptan treatment to start the Lixivaptan Re-titration Period (1 to 2 weeks). During the Lixivaptan Re-titration Period, participants will have their dose of lixivaptan re-established based on the dose they were receiving at the completion of the lead-in study. Participants will continue on lixivaptan treatment for up to 104 weeks during the Maintenance Treatment Period and will be assessed at a study visit every 12 weeks. In between the quarterly study visits, participants will be required to have blood drawn for liver chemistry determinations every 4 weeks. At the end of 104 weeks, lixivaptan treatment will be stopped, and participants will enter a 4-week Follow-up Period during which final assessments of safety and efficacy will be obtained over 3 visits during a 28-day period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group, open-label study
| Arm | Type | Receives |
|---|---|---|
| Lixivaptan | Experimental | Drug: LixivaptanLixivaptan capsules 100-200mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female participants with ADPKD who completed study PA-ADPKD-303
- Continued control of hypertension without the use of a diuretic
- Continued adherence to prohibitions on concomitant medications stated in the study PA-ADPKD-303 protocol
- 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.
Key exclusion criteria (9 listed)
- Any contraindication to continued treatment with lixivaptan
- 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 participant
- Hypovolemia on physical examination at Screening
- The following laboratory results based on serum drawn at Visit 24 of PA-ADPKD-303:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LixivaptanOral vasopressin V2 receptor antagonist | Drug | Lixivaptan |
Primary outcome
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
Time frame: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of participants who develop serum alanine aminotransferase (ALT) levels >3 × the upper limit of normal (ULN) which are assessed by the independent Hepatic Events Review Committee (HERC) to be at least probably related to lixivaptan and resulted in discontinuation of lixivaptan treatment. The independent HERC, after reviewing demographic, medical and medication history, safety data and other relevant data of participants who develop liver abnormalities, will determine the probable causality for liver chemistry test abnormalities of concern and the relatedness to lixivaptan using the Drug-Induced Liver Injury Network probability criteria (Fontana et al., 2009). The normal range of ALT was defined as 0-55 U/L.
7 secondary outcomes
Number of Participants Who Develop Serum ALT Levels >5 x ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment
Time frame: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of Participants Who Develop Serum ALT Values >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Dose Reduction of Lixivaptan Treatment
Time frame: 120 days (from Screening to the end of the Maintenance Treatment Period)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important Clinical Laboratory Findings
Time frame: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important Vital Signs Findings
Time frame: 140 days (from Screening to the end of the Follow-up Period)
Number of Participants With Potentially Clinically Important 12-lead Electrocardiogram (ECG) Findings
Time frame: 140 days (from Screening to the end of the Follow-up Period)
Annualized Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Final Assessment
Time frame: 140 days (from Screening to the end of the Follow-up Period)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19132805Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J, Rochon J; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf. 2009;32(1):55-68. doi: 10.2165/00002018-200932010-00005.
- Individual participant dataSharing planned: No
Related trials for Polycystic Kidney Disease, Adult
RecruitingObservational study
Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
Active, not recruitingObservational study
Role of ROS and cAMP-PKA Biomarkers in ADPKD
Autosomal Dominant Polycystic Kidney Disease
Not yet recruitingPhase 1
A Study to Investigate the Pharmacokinetics of JMKX003142 in Healthy Participants and Participants With Hepatic Impairment
ADPKD (Autosomal Dominant Polycystic Kidney Disease), Renal Edema
RecruitingPhase 1
Absorption, Distribution, Metabolism, and Excretion of 14C-VX-407 After a Single Oral Dose
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nelson Kopyt, DO principal investigator
Northeast Clinical Research Center, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lixivaptan in people with Polycystic Kidney Disease, Adult, run by Palladio Biosciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Develop Serum ALT Levels >3 × ULN During the Lixivaptan Re-titration or Maintenance Treatment Periods Assessed to be Related to Lixivaptan and Resulted in Discontinuation of Lixivaptan Treatment (time frame: 120 days (from Screening to the end of the Maintenance Treatment Period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05208866, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023.