Clinical Trials

Numerous clinical trials evaluate the efficacy, safety, and pharmacokinetics of tolvaptan across Phase 1 through Phase 4 studies. Primary conditions evaluated include hyponatremia associated with SIADH or cirrhosis, autosomal dominant polycystic kidney disease, and acute decompensated heart failure. Sponsored by pharmaceutical entities and academic institutions, these trials encompass various recruitment statuses, ranging from completed and actively recruiting to terminated or unknown.

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04782258 RECRUITING
Autosomal Recessive Polycystic Kidney (ARPKD)
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2023-01-23 PHASE3
NCT04786574 WITHDRAWN
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2022-07-01 PHASE3
NCT05190744 COMPLETED
Autosomal Dominant Polycystic Kidney Disease; Nephrogenic Diabetes Insipidus; Acquired Nephrogenic Diabetes Insipidus; Congenital Nephrogenic Diabetes Insipidus
Mayo Clinic
 2022-09-01 PHASE2
NCT06506994 COMPLETED
Heart Failure With Volume Overload
Fujian Shengdi Pharmaceutical Co., Ltd.
 2024-08-16 PHASE1
NCT06171100 Recruiting
Hyponatremia|SIADH
King''s College Hospital NHS Trust
 2024-03-15 --
NCT04331132 UNKNOWN
Acute Heart Failure
Gia Dinh People Hospital
 2021-12-01
NCT05569655 UNKNOWN
Pulmonary Arterial Hypertension; Randomized Controlled Trial
Chinese Pulmonary Vascular Disease Research Group
 2021-04-06
NCT05060523 UNKNOWN
Liver Cirrhosis
Institute of Liver and Biliary Sciences, India
 2021-09-19
NCT04152837 TERMINATED
Polycystic Kidney Disease, Adult; ADPKD
Palladio Biosciences
 2020-09-02 PHASE3
NCT03949894 COMPLETED
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Korea Otsuka Pharmaceutical Co., Ltd.
 2019-07-01 PHASE4
NCT03541447 COMPLETED
Autosomal Dominant Polycystic Kidney Disease
Mario Negri Institute for Pharmacological Research
 2018-12-12 PHASE2
NCT02964273 COMPLETED
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2016-09-23 PHASE3
NCT03764605 UNKNOWN
ADPKD
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
 2019-01-30 PHASE3
NCT03858439 COMPLETED
Polyuria; Autosomal Dominant Polycystic Kidney
McMaster University
 2019-06-06
NCT03255226 COMPLETED
Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload
Otsuka Pharmaceutical Co., Ltd.
 2018-03-07 PHASE3
NCT02476409 COMPLETED
Congestive Heart Failure
University of North Carolina, Chapel Hill
 2015-07 PHASE4
NCT03931369 UNKNOWN
Healthy Volunteers
Assistance Publique - Hôpitaux de Paris
 2019-09-06 PHASE2
NCT02729662 UNKNOWN
Autosomal Dominant Polycystic Kidney Disease
Kyorin University
 2016-10-01
NCT03772041 COMPLETED
Congestive Heart Failure
Otsuka Pharmaceutical Co., Ltd.
 2019-01-16 PHASE3
NCT02959411 TERMINATED
Heart Failure; Hyponatremia
University of Calgary
 2016-10 PHASE4
NCT02666651 UNKNOWN
Decompensated Heart Failure; Hyponatremia
Cardiology Research UBC
 2016-05 PHASE4
NCT04182958 Completed
Healthy Adult Male
Otsuka Pharmaceutical Co. Ltd.
 2019-11-25 Phase 1
NCT03596957 UNKNOWN
Autosomal Dominant Polycystic Kidney
Lisbet Brandi
 2018-09-12 PHASE4
NCT03048747 COMPLETED
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Otsuka Pharmaceutical Co., Ltd.
 2017-03-02 PHASE3
NCT02646540 COMPLETED
Cardiomyopathy; Congestive Heart Failure
Emory University
 2016-01 PHASE1
NCT02538016 COMPLETED
Cystinuria
Caleb Nelson
 2016-10
NCT02251275 COMPLETED
Polycystic Kidney, Autosomal Dominant
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2014-10-17 PHASE3
NCT02606253 COMPLETED
Heart Failure
Vanderbilt University
 2016-02 PHASE4
NCT03254108 COMPLETED
Congestive Heart Failure
Otsuka Pharmaceutical Co., Ltd.
 2017-11-06
NCT02183792 COMPLETED
Heart Failure
University of Southern California
 2014-12 PHASE4
NCT03803124 COMPLETED
Polycystic Kidney, Autosomal Dominant
Regional Hospital Holstebro
 2015-12 PHASE3
NCT02020278 TERMINATED
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2016-04-22 PHASE3
NCT02012959 TERMINATED
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2015-09-22 PHASE3
NCT02442674 WITHDRAWN
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2015-11 PHASE3
NCT02160145 COMPLETED
Chronic Kidney Disease; Autosomal Dominant Polycystic Kidney Disease
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2014-05 PHASE3
NCT02352285 TERMINATED
Heart Failure With Hyponatremia
Korea Otsuka Pharmaceutical Co., Ltd.
 2012-12 PHASE4
NCT02994394 Completed
Healthy Adult Male
Otsuka Pharmaceutical Co. Ltd.
 2017-01-06 Phase 1
NCT02644616 COMPLETED
Tricuspid Regurgitation; Right Heart Failure
Shanghai Chest Hospital
 2014-11 PHASE4
NCT02729662 Unknown status
Autosomal Dominant Polycystic Kidney Disease
Kyorin University
 2016-10-01 Not Applicable
NCT02527863 COMPLETED
Autosomal Dominant Polycystic Kidney Disease
Regional Hospital Holstebro
 2015-02 PHASE2
NCT01584557 COMPLETED
Heart Failure
Cardiovascular Clinical Sciences Inc
 2012-06 PHASE3
NCT02545114 TERMINATED
Hyponatremia; SIADH
Polderman, Kees, H., MD, PhD
 2015-08
NCT02331680 COMPLETED
Chronic Renal Failure
Otsuka Pharmaceutical Co., Ltd.
 2014-12 PHASE2
NCT02020278 Terminated
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization Inc.|Syneos Health
 2016-04-22 Phase 3
NCT02173288 COMPLETED
Cirrhosis; Refractory/Recurrent Ascites
Post Graduate Institute of Medical Education and Research, Chandigarh
 2013-07 PHASE2; PHASE3
NCT01214421 COMPLETED
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2010-05-26 PHASE3
NCT01644331 COMPLETED
Heart Failure; Dyspnea
Duke University
 2012-10 PHASE3
NCT02078973 COMPLETED
Nephropathy
Regional Hospital Holstebro
 2014-03-01 PHASE2
NCT01863511 COMPLETED
Acute Decompensated Heart Failure
The Christ Hospital
 2013-05 PHASE4
NCT01973140 COMPLETED
Healthy
Northwestern University
 2013-11 PHASE4
NCT02096965 COMPLETED
Nephrolithiasis, Calcium Oxalate; Nephrolithiasis, Calcium Phosphate
Mayo Clinic
 2014-03 PHASE1
NCT02009878 COMPLETED
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2013-11 PHASE1; PHASE2
NCT01890694 TERMINATED
Hyponatremia
NYU Langone Health
 2012-03 PHASE4
NCT01425125 WITHDRAWN
Cerebral Hyponatremia; SIADH; Cerebral Salt-wasting Syndrome; Reset Hypothalamic Osmostat
NYU Langone Health
 2011-11
NCT01292304 COMPLETED
Ascites; Cirrhosis
University of Florida
 2012-03 PHASE4
NCT03910231 COMPLETED
Healthy
Brigham and Women's Hospital
 2012-02-01 PHASE1
NCT01280721 COMPLETED
Autosomal Dominant Polycystic Kidney Disease （ADPKD)
Otsuka Pharmaceutical Co., Ltd.
 2010-11 PHASE3
NCT01618448 COMPLETED
Cardiac-induced Edema
Taiwan Otsuka Pharm. Co., Ltd
 2012-07 PHASE3
NCT01439009 COMPLETED
Heart Failure
Otsuka Pharmaceutical Co., Ltd.
 2011-09 PHASE4
NCT01638663 COMPLETED
Cardiovascular Diseases; Nephropathy
Regional Hospital Holstebro
 2012-05 PHASE2
NCT01346072 COMPLETED
Cardiovascular Diseases; Heart Diseases; Heart Failure
University of North Carolina, Chapel Hill
 2011-04 PHASE4
NCT01716611 UNKNOWN
Hyponatremia; Ascites
Konkuk University Medical Center
 2012-11 PHASE4
NCT01663662 WITHDRAWN
Heart Failure
University of Michigan
 2012-08 PHASE4
NCT01199198 COMPLETED
Advanced Cancers
M.D. Anderson Cancer Center
 2011-05 PHASE4
NCT01451827 COMPLETED
Autosomal Dominant Polycystic Kidney Disease
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2011-10 PHASE2
NCT01651156 COMPLETED
Cardiac Edema
Otsuka Beijing Research Institute
 2012-07 PHASE3
NCT01556646 COMPLETED
Cirrhosis; Hepatic Encephalopathy; Hyponatremia
Hunter Holmes Mcguire Veteran Affairs Medical Center
 2011-04 PHASE3
NCT01227512 TERMINATED
Hyponatremia; Dilutional Hyponatremia; Inappropriate ADH Syndrome
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2010-10 PHASE3
NCT01386372 TERMINATED
Hyponatremia
Mario Negri Institute for Pharmacological Research
 2011-06 PHASE2
NCT01507727 UNKNOWN
Non-hypovolemic Non-acute Hyponatremia
Jiangsu HengRui Medicine Co., Ltd.
 2012-01 PHASE2; PHASE3
NCT01349348 COMPLETED
Ascites; Hepatic Cirrhosis
Otsuka Beijing Research Institute
 2010-10 PHASE3
NCT01552590 TERMINATED
Hyponatremia and Extracellular Fluid in Cirrhotic
Korea Otsuka Pharmaceutical Co., Ltd.
 2012-04 PHASE4
NCT01261481 COMPLETED
Healthy
University of North Carolina, Chapel Hill
 2011-01 PHASE1
NCT00428948 COMPLETED
Polycystic Kidney Disease, Autosomal Dominant
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2007-01 PHASE3
NCT01336972 COMPLETED
Autosomal Dominant Polycystic Kidney Disease
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2010-10 PHASE2
NCT07166887 COMPLETED
Healthy Subjects
Otsuka Beijing Research Institute
 2011-06-07 PHASE1
NCT07166783 COMPLETED
Health Subjects
Otsuka Beijing Research Institute
 2011-06-16 PHASE1
NCT01210560 COMPLETED
Autosomal Dominant Polycystic Kidney Disease
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2010-10 PHASE2
NCT00413777 COMPLETED
Polycystic Kidney, Autosomal Dominant
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2005-12 PHASE2
NCT01014416 COMPLETED
Healthy
Korea Otsuka Pharmaceutical Co., Ltd.
 2010-01 PHASE1
NCT00664014 COMPLETED
Hypovolemic Hyponatremia
Otsuka Beijing Research Institute
 2008-05 PHASE2
NCT01349335 COMPLETED
Ascites; Hepatic Cirrhosis
Otsuka Beijing Research Institute
 2009-04 PHASE2
NCT01359462 COMPLETED
Hepatic Cirrhosis; Ascites
Otsuka Beijing Research Institute
 2009-04 PHASE1
NCT02449044 COMPLETED
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2004-05 PHASE3
NCT00550459 COMPLETED
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2007-08 PHASE3
NCT00544869 COMPLETED
Cardiac Edema
Otsuka Pharmaceutical Co., Ltd.
 2007-10 PHASE3
NCT00525265 COMPLETED
Cardiac Edema
Otsuka Pharmaceutical Co., Ltd.
 2007-09 PHASE3
NCT00462670 COMPLETED
Edema, Cardiac
Otsuka Pharmaceutical Co., Ltd.
 2007-04 PHASE3
NCT07166796 COMPLETED
Health Subjects
Otsuka Beijing Research Institute
 2006-10-01 PHASE1
NCT00132886 COMPLETED
Heart Failure, Congestive
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2004-12 PHASE2
NCT00071331 COMPLETED
Congestive Heart Failure
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2003-09 PHASE3
NCT00234104 COMPLETED
Heart Failure, Congestive; Edema
Otsuka Pharmaceutical Co., Ltd.
 2004-08 PHASE2
NCT00072683 COMPLETED
Hyponatremias; Water Intoxication; Inappropriate ADH Syndrome; Water-Electrolyte Imbalances
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2003-04-01 PHASE3
NCT00201994 COMPLETED
Hyponatremia
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2003-11-01 PHASE3
NCT00043758 COMPLETED
Congestive Heart Failure
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2002-07 PHASE2
NCT01733134 WITHDRAWN
Acute Heart Failure
Maisel, Alan, M.D.
 PHASE3
NCT00043771 COMPLETED
Congestive Heart Failure
Otsuka Pharmaceutical Development & Commercialization, Inc.
 2002-05 PHASE2

(data from https://clinicaltrials.gov, updated on 2026-08-07)

Check the Tolvaptan product page for in-depth specifications, including solubility, stock solutions, MOA, and working concentrations.

Compliance for Clinical Use

Mechanism and Biochemical Profile

Tolvaptan selectively and competitively binds to the arginine vasopressin V2 receptor, blocking vasopressin-induced intracellular signaling and water reabsorption in the renal collecting duct. This aquaretic inhibition promotes solute-free water excretion without altering electrolyte balance, thereby elevating serum sodium concentrations in clinical trial conditions including hyponatremia, heart failure, and autosomal dominant polycystic kidney disease.

Appendix RUO and cGMP Quality Standards

Quality Dimension RUO (Research Use Only) cGMP (Current Good Manufacturing Practice)
Clinical Applicability Prohibited in human clinical trials or medical diagnostics. Mandatory for human clinical trials (Phase I–III) and therapies.
Regulatory Status Non-regulated grade; exempt from drug manufacturing laws. Legally enforced by health authorities (e.g., FDA, EMA, NMPA).
Facility Environment Unclassified analytical or research laboratories. Validated Cleanrooms (ISO Class 5–8) with continuous monitoring.
Quality Control Basic purity and activity testing. Rigorous safety release testing (Sterility, Endotoxin, Mycoplasma).
Process Validation Basic equipment calibration; no process validation required. Full qualification (IQ/OQ/PQ) and complete batch records.
Quality Assurance Vendor self-declared without required formal QMS. Mandatory QA/QC unit, Change Control, CAPA, and vendor audits.
Regulatory Impact High risk of IND rejection if used as a critical raw material. Required for IND/NDA filings, supported by Drug Master Files (DMF).

Footnotes

Regulatory Note: Governed by FDA (21 CFR Parts 210/211/312), EMA (EudraLex Vol 4), ICH Guidelines (E6/Q7/Q9/Q10), and compendial standards (USP <71>/<85>/<1043>).

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Note: Technical data last updated: Sep 1, 2026.