Autosomal Dominant Polycystic Kidney DiseasePhase 2SerendipityPB1NCT05190744
Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
A Phase 2 study testing PB in people with Autosomal Dominant Polycystic Kidney Disease and Nephrogenic Diabetes Insipidus, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this research is to study the effectiveness and safety of the medication PB in slowing the frequent urination related to tolvaptan as long-term treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), or frequent urination related to inherited nephrogenic diabetes insipidus as an inherited… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus, Acquired Nephrogenic Diabetes Insipidus
- What is being tested?
- PB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 8 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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, ≥ 18 years of age (inclusive) at time of screening
- Diagnosis of one of the following:
- ADPKD(as delineated in cohort 1)
- Congenital NDI (as delineated in cohort 1)
- Lithium-induced NDI (as delineated in cohort 1)
- Glomerular filtration rate (GFR) ≥ 25 ml/min/1.73 m2 at time of screening visit calculated as in cohort
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- 24 hours urine volume in baseline 1 visit ≥ 5000 ml/ day
- If hypertensive, blood pressure controlled on antihypertensives (<130/80 mm Hg) at least 30 days before day 1. Antihypertensives may be adjusted at time of baseline 2 per PI discretion.
- Female participants (see details in cohort 1 inclusion criteria)
- Have read, understood, and provided written informed consent after the nature of the study has been fully explained and must be willing to comply with protocol requirements and study-related procedures.
- Negative urinary pregnancy test (if applicable) at baseline 2
- Capable of providing urine samples as dictated by the protocol
Who cannot join
- Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant kidney disease, kidney cancer, transplanted kidney, single kidney, kidney surgery within the past 6 months (including cyst drainage or fenestration) or acute kidney injury within 6 months prior to screening.
- Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia).
- Other significant chronic medical disease (heart failure, diabetes mellitus, liver disease, transient or persistent elevated transaminases)
- History of acute gout attack in the past 30 days
- History of clinically significant drug or alcohol abuse in the 2 years prior to screening visit.
- Uncontrolled hyperuricemia or active gout
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- History of hepatotoxicity related to tolvaptan; or clinically significant liver disease or impairment; or alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin values >1.2 x Upper Limit of Normal (ULN) during screening.
- 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.
- Requirement for ongoing diuretic use.
- Participants who are currently taking, 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. If applicable, there should be a 14-day washout of these treatments prior to Day 1.
- Prior use of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) (e.g., canagliflozin, dapagliflozin, empagliflozin, etc.) within the 2 months prior to screening visit or expected need for initiation of treatment with a SGLT2i inhibitor during the study. Current use of SGLT2i will be reviewed by PI and allow enrollment if patient has been on stable dose for at least 2 months.
- Prior use of a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor within the 2 months prior to screening visit or expected need for initiation of treatment with a HIF-PH inhibitor during the study;
- Participants who have taken any investigational drug or used an investigational device within 30 days, or 5 half-lives, whichever is longer, prior to screening visit 1a or plan to participate in an interventional trial during the study.
- Allergy to probenecid
- History of persistent hyponatremia
- Positive test results for hepatitis B surface antigen (HBsAg).
- Positive test results for hepatitis C (HCV) antibody (Anti-HCV), with the exception of participants for whom the reflex HCV RNA titer test is negative.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi-center, Open-Label, Exploratory Study to Assess the Efficacy of PB in Decreasing the Urine Output and Increasing the Urine Osmolality in Patients With Hereditary Nephrogenic Diabetes Insipidus, Patients With Autosomal Dominant Polycystic Kidney Disease Treated With Tolvaptan, And Severely Polyuric Patients With Previous Lithium Administration (Serendipity-PB1)
The purpose of this research is to study the effectiveness and safety of the medication PB in slowing the frequent urination related to tolvaptan as long-term treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), or frequent urination related to inherited nephrogenic diabetes insipidus as an inherited condition or as an acquired condition from prior treatment with lithium.
- Conditions
- Autosomal Dominant Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus, Acquired Nephrogenic Diabetes Insipidus, Congenital Nephrogenic Diabetes Insipidus
- Being tested
- PB
- Keywords
- Tolvaptan, ADPKD, Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus (NDI), Nephrogenic diabetes insipidus, Inherited nephrogenic diabetes insipidus, Diabetes Insipidus, Lithium, Lithium-induced nephrogenic diabetes insipidus, Vasopressin receptor antagonist, Tolvaptan-induced aquaresis
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Diabetes Insipidus, Nephrogenic, Polycystic Kidney Diseases, Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBDrug
1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance.
| Study group | Role | What they receive |
|---|---|---|
| Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus | Experimental | Polyuric subjects with hereditary nephrogenic diabetes insipidus with loss of function of arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) will be treated with PB Receives: Drug: PB |
| Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan | Experimental | Polyuric subjects with autosomal dominant polycystic kidney disease on chronic tolvaptan treatment will be treated with PB Receives: Drug: PB |
| Polyuric subject secondary to lithium administration | Experimental | Polyuric subject post lithium administration will receive PB Receives: Drug: PB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in urine osmolality
Measured in milliosmoles per kilogram of water (mOsm/kg) from a urine specimen and is a measure of the concentration of osmotically active particles, principally sodium, chloride, potassium, and urea
Measured: Baseline, 30 days
Secondary outcomes (1)
Change in urine output
Measured in milliliters per day (ml/day) by 24 hour urine collection
Measured: From Baseline 2 to Post Treatment Follow Up at the end of 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start1 Sep 2022
- Primary completion8 Dec 2025
- Study completion8 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka America Pharmaceutical
- Responsible party
- Principal investigator, Fouad T. Chebib, Mayo Clinic
- Investigators
- Fouad Chebib, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05190744
- Sponsor's protocol ID
- 21-005437
- Acronym
- SerendipityPB1
- Status last verified
- Jan 2026
- First submitted
- 29 Dec 2021
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open-Label, Exploratory Study to Assess the Efficacy of PB in Decreasing the Urine Output and Increasing the Urine Osmolality in Patients With Hereditary Nephrogenic Diabetes Insipidus, Patients With Autosomal Dominant Polycystic Kidney Disease Treated With Tolvaptan, And Severely Polyuric Patients With Previous Lithium Administration (Serendipity-PB1)
- ClinicalTrials.gov ID
- NCT05190744
- Acronym / sponsor ID
- SerendipityPB1 / 21-005437
- Conditions
- Autosomal Dominant Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus, Acquired Nephrogenic Diabetes Insipidus, Congenital Nephrogenic Diabetes Insipidus
- Keywords
- Tolvaptan, ADPKD, Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus (NDI), Nephrogenic diabetes insipidus, Inherited nephrogenic diabetes insipidus, Diabetes Insipidus, Lithium
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Otsuka America Pharmaceutical
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 8 Dec 2025 (actual)
- Study completion
- 8 Dec 2025 (actual)
- First posted
- 13 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to study the effectiveness and safety of the medication PB in slowing the frequent urination related to tolvaptan as long-term treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), or frequent urination related to inherited nephrogenic diabetes insipidus as an inherited condition or as an acquired condition from prior treatment with lithium.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus | Experimental | Drug: PBPolyuric subjects with hereditary nephrogenic diabetes insipidus with loss of function of arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) will be treated with PB |
| Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan | Experimental | Drug: PBPolyuric subjects with autosomal dominant polycystic kidney disease on chronic tolvaptan treatment will be treated with PB |
| Polyuric subject secondary to lithium administration | Experimental | Drug: PBPolyuric subject post lithium administration will receive PB |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female, ≥ 18 years of age (inclusive) at time of screening
- Diagnosis of one of the following:
- Glomerular filtration rate (GFR) ≥ 25 ml/min/1.73 m2 at time of screening visit calculated as in cohort
- 24 hours urine volume in baseline 1 visit ≥ 5000 ml/ day
- If hypertensive, blood pressure controlled on antihypertensives (<130/80 mm Hg) at least 30 days before day 1. Antihypertensives may be adjusted at time of baseline 2 per PI discretion.
Key exclusion criteria (17 listed)
- Advanced diabetes (e.g., glycosylated hemoglobin [HgbA1c] >7.5%, and/or glycosuria by dipstick, significant proteinuria [>300 mcg albumin/mg creatinine]), other significant kidney disease, kidney cancer, transplanted kidney, single kidney, kidney surgery within the past 6 months (including cyst drainage or fenestration) or acute kidney injury within 6 months prior to screening.
- Clinically significant incontinence, overactive bladder, or urinary retention (e.g., benign prostatic hyperplasia).
- Other significant chronic medical disease (heart failure, diabetes mellitus, liver disease, transient or persistent elevated transaminases)
- History of acute gout attack in the past 30 days
- History of clinically significant drug or alcohol abuse in the 2 years prior to screening visit.
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 |
|---|---|---|
| PB1000mg twice daily (BID). The dose of PB inducing the maximal increase in urine osmolality will be continued for up to four weeks providing that no side effects are observed including clinical and laboratory surveillance. | Drug | Polyuric subject secondary to lithium administration, Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan, Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus |
Primary outcome
Change in urine osmolality
Time frame: Baseline, 30 days
Measured in milliosmoles per kilogram of water (mOsm/kg) from a urine specimen and is a measure of the concentration of osmotically active particles, principally sodium, chloride, potassium, and urea
1 secondary outcome
Change in urine output
Time frame: From Baseline 2 to Post Treatment Follow Up at the end of 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Fouad Chebib, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PB in people with Autosomal Dominant Polycystic Kidney Disease and Nephrogenic Diabetes Insipidus, run by Mayo Clinic 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 12 inclusion and 17 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: finished, as of the sponsor's last update on 27 Jan 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in urine osmolality (time frame: Baseline, 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2026.