PB to Treat Hereditary Nephrogenic Diabetes Insipidus, ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Autosomal Dominant Polycystic Kidney Disease, Nephrogenic Diabetes Insipidus, Acquired Nephrogenic Diabetes Insipidus, Congenital Nephrogenic Diabetes Insipidus

Intervention / Treatment
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* Drug: PB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of nephrogenic diabetes insipidus (NDI) (congenital, tolvaptan-induced, or lithium-induced). Morning Uosm < 300 mOsm/kg H2O. Participating in tolvaptan arm. Males for NDI. Autosomal Dominant Polycystic Kidney Disease (ADPKD). Lithium-induced NDI. GFR ≥ 30 ml/min. If hypertensive, blood pressure controlled on antihypertensives (< 130/80 mm Hg) at least 30 days before day 1. Capable of providing consent. Capable of providing urine samples as dictated by the protocol. Exclusion Criteria: History of acute gout attack in the past 30 days. Uncontrolled hyperuricemia or active gout. Known urinary retention, urinary incontinence or bladder dysfunction. Other significant chronic medical disease (heart failure, diabetes mellitus, liver disease, transient or persistent elevated transaminases. History of hepatotoxicity related to tolvaptan. Allergy to interventional drug (PB). History of persistent hyponatremia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus<br>Polyuric subjects with hereditary nephrogenic diabetes insipidus with loss of function of AVPR2 or AQP2 will be treated with PB | Drug: PB<br>* 500mg BID followed by 1000mg BID. The dose of PB inducing the maximal increase in urine osmolality will be continued for up to three months providing that no side effects are observed including clinical and laboratory surveillance.<br>|
| Experimental: Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan<br>Polyuric subjects with autosomal dominant polycystic kidney disease on chronic tolvaptan treatment will be treated with PB | Drug: PB<br>* 500mg BID followed by 1000mg BID. The dose of PB inducing the maximal increase in urine osmolality will be continued for up to three months providing that no side effects are observed including clinical and laboratory surveillance.<br>|
| Experimental: Polyuric subject secondary to lithium administration<br>Polyuric subject post lithium administration will receive PB | Drug: PB<br>* 500mg BID followed by 1000mg BID. The dose of PB inducing the maximal increase in urine osmolality will be continued for up to three months providing that no side effects are observed including clinical and laboratory surveillance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline, 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine output | Measured in milliliters per day (ml/day) by 24 hour urine collection | Baseline, day 15, day 45, day 75 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tolvaptan, ADPKD, Polycystic Kidney Disease, NDI, Nephrogenic diabetes insipidus, Inherited nephrogenic diabetes insipidus, Diabetes Insipidus, Lithium, Lithium-induced nephrogenic diabetes insipidus, Vasopressin receptor antagonist, Tolvaptan-induced aquaresis