A Phase 3 interventional study of Tolvaptan and Placebo in Hyponatremia, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-13.
Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. (part of Otsuka Holdings Co., Ltd.) · Phase 3, Interventional, and Treatment
The purpose of this study was to determine whether tolvaptan can safely and effectively return the body's balance of sodium and water toward normal and to characterize and quantify the potential clinical benefits of this treatment.
Hyponatremia is defined as a serum sodium concentration below the lower limit of normal and is the most frequently encountered electrolyte abnormality in hospitalized patients. Generally speaking, most cases of hyponatremia are mild. However, as the serum sodium falls below 130 mEq/L, the possibility of significant morbidity and mortality increases, and most clinicians will initiate corrective therapy for serum sodium values approaching 130 mEq/L and lower. The reasons for treating hyponatremia relate both to the symptoms, which may be quite disturbing to patients, as well as to potential outcomes including permanent neurological damage and death. There is also growing awareness of the association between hyponatremia and increased mortality in patients with heart failure.
A common theme underlying the occurrence of hyponatremia, whether in the setting of congestive heart failure, hepatic failure with ascites, or the syndrome of inappropriate anti-diuretic hormone (SIADH), is the non-osmotic secretion of arginine vasopressin (AVP). The presence of excess AVP leads to fluid retention and hyponatremia. Agents that antagonize AVP, causing proportionally more water diuresis than solute excretion, could offer a significant treatment option for patients with hyponatremia, compared to fluid restriction alone. Treatment of hyponatremia, particularly in clinical settings such as decompensated congestive heart failure, is difficult, as conventional diuretics cause neurohormonal activation and further stimulate the inappropriate release of vasopressin, leading to additional retention of free water and aggravation of hypo-osmolality. Similarly, for cirrhosis with ascites and SIADH, conventional diuretics are either minimally effective or completely contraindicated. An alternative approach to symptom relief and treatment of hyponatremia may be the use of vasopressin antagonists, which increase free water clearance with proportionally less effect on sodium excretion. Tolvaptan is an oral vasopressin antagonist with relative affinity for the V2 receptor which has been shown to induce a diuresis with proportionally more free-water than sodium loss.
The current study was conducted to evaluate whether tolvaptan, an oral AVP inhibitor, was effective in correcting mild to moderate hyponatremia and to elucidate the effect of this correction on the subject's well-being.
164 studies on the registry are indexed under Hyponatremia; 16 are open to participants now.
This study's enrollment of 243 is above the median of 60 across 98 interventional studies indexed under Hyponatremia.
Browse Hyponatremia studies →Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 295 studies on the registry; 18 are open to participants now.
Of its 106 completed or terminated interventional studies of FDA-regulated products, 71 (67%) have results posted.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received tolvaptan orally once a day for 30 days. Initially participants received tolvaptan 15 mg and were forced titrated to 30 mg and 60 mg based on the change in their serum sodium level. Titration occurred if the serum sodium level increased by \< 5 mEq/L (mmol/L) from the previous measurement 22-24 hours earlier and was ≤ 135 mEq/L (mmol/L).
Drug: Tolvaptan
Participants received placebo orally once a day for 30 days.
Drug: Placebo
Tolvaptan was supplied as tablets.
Also known as: Samsca, OPC-41061
Placebo was supplied as tablets.
Plan to share: Yes — Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
Access criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
Data sharing details ↗ · clinical-trials.otsuka.com
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tolvaptan
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