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Evidence: MediumSmall molecule, not a peptideDiscontinuedNot a peptideVasopressin V2 blockerDevelopment stopped 2022

Lixivaptan

An oral vasopressin receptor blocker that raised sodium in hyponatraemia trials, then was dropped for kidney disease after a liver signal

Lixivaptan is a small molecule, not a peptide, that blocks the vasopressin V2 receptor so the kidneys release free water. Phase 3 trials raised low blood sodium. Its last developer stopped work on it in June 2022 after liver enzyme rises in one patient.

At a Glance Read Research →
Overview

What is it?

Vasopressin tells the kidneys to hold on to water. When too much of it acts, blood sodium is diluted, the condition called hyponatraemia. Blocking the V2 receptor makes the kidneys release water without salt, which raises sodium. Tolvaptan is the approved drug of this kind; lixivaptan is a related oral molecule. Despite appearing in this encyclopedia, it is not a peptide.

Its phase 3 trials worked. In hospitalised patients with euvolaemic hyponatraemia, sodium rose 6.7 mmol/l by day 7 against 4.5 on placebo; in 206 outpatients it rose 3.2 against 0.8, and 39.4% reached normal sodium against 12.2%. In heart failure with fluid overload, 100 mg daily reduced weight and improved breathlessness.

Its developer later turned it to polycystic kidney disease, where tolvaptan's liver toxicity leaves room for an alternative, and tested it in patients who had stopped tolvaptan for that reason. On June 2, 2022, Centessa stopped all development, citing liver enzyme elevations in one such patient alongside cost and commercial reassessment.

It was never approved anywhere. Development for hyponatraemia had already ended.

+6.7 mmol/l
Sodium by day 7
vs +4.5 placebo, inpatients
39.4% vs 12.2%
Reached normal sodium
outpatients, day 7
June 2022
Development stopped
Centessa
Structured data

At a Glance

Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.

ClassAn oral selective V2 vasopressin receptor antagonist (aquaretic) for hyponatremia and polycystic kidney disease.
SequenceNon-peptide small molecule (vasopressin V2 receptor antagonist)
FormulaC27H29ClN4O2
Molecular weight476.0 g/mol
Half-lifenot reported in the sources read
Studied dose25–100 mg (twice daily, oral)
US statusDiscontinued
Evidence levelMedium
Last reviewed2026-09-30

Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Evidence

Published Research

These are the trials that describe lixivaptan, read from their PubMed abstracts: two phase 3 hyponatraemia trials, a heart-failure trial and an early dose-ranging study.

Human2012

Hospitalised hyponatraemia

Patients with euvolaemic hyponatraemia took 50 mg then 25 to 100 mg daily, titrated to sodium, for 30 days. Sodium rose 6.7 mmol/l by day 7 against 4.5 on placebo and normalised faster, then fell back to near baseline within 7 days of stopping.

PMID: 22932119
Human2012

Outpatient hyponatraemia

206 outpatients, about half elderly in chronic care, took 25 to 100 mg daily or placebo. Sodium rose 3.2 mmol/l by day 7 against 0.8, and 39.4% reached normal sodium against 12.2%.

PMID: 22932122
Human2012

Heart failure with fluid overload

170 outpatients took 100 mg daily or placebo on top of standard therapy. Weight fell from day 1, breathlessness and orthopnoea improved, and thirst and frequent urination were commoner on the drug.

PMID: 22510424
Human2006

Dose finding in heart failure

Single doses of 10 to 400 mg raised 24-hour urine volume from 1.8 litres on placebo to 3.9 litres at the top dose, with more free-water excretion and, at higher doses, higher sodium.

PMID: 16630999
Review2012

Vaptans in cirrhosis

A meta-analysis of 12 trials (2,266 patients) of tolvaptan, satavaptan and lixivaptan in cirrhosis found sodium rose by about 1.8 mmol/L and ascites eased, with no effect on mortality or complications and four times the adverse events, including excessive urine output.

PMID: 22908905
Safety

Side Effects & Contraindications

Reported Side Effects

From the trials above and the reason development stopped.

● Thirst and frequent urination, the expected effects of releasing water
● Sodium can rise too quickly, which is why trials titrated and monitored it
● Liver enzyme elevations in one patient with polycystic kidney disease, cited when development stopped

Contraindications & Cautions

No product exists to take.

● Anyone seeking it — development stopped in 2022 and it was never approved
● Use without sodium monitoring, the risk with every vaptan
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?Is lixivaptan a peptide?

No. It is a small-molecule vasopressin receptor blocker taken by mouth, related to tolvaptan.

?What did it do?

It made the kidneys release free water, raising low blood sodium in phase 3 trials.

?Why was it dropped?

In June 2022 Centessa stopped development after liver enzyme rises in one patient, citing cost and commercial reassessment too.

?Is it approved anywhere?

No. It was never approved, and development has ended.

Bibliography

References

  1. [pubmed] Abraham WT, et al. "Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia." Kidney Int, 2012;82(11):1223-30. PMID: 22932119.
  2. [pubmed] Abraham WT, et al. "Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia." Kidney Int, 2012;82(11):1215-22. PMID: 22932122.
  3. [pubmed] Ghali JK, et al. "The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study." Eur J Heart Fail, 2012;14(6):642-51. PMID: 22510424.
  4. [pubmed] Abraham WT, et al. "Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients." J Am Coll Cardiol, 2006;47(8):1615-21. PMID: 16630999.
  5. [other] Centessa Pharmaceuticals plc, Form 8-K and press release, June 2, 2022: strategic decision to discontinue clinical development of lixivaptan for ADPKD. Read September 30, 2026.
  6. [clinicaltrials] ClinicalTrials.gov NCT04064346: ACTION, the phase 3 trial of lixivaptan in autosomal dominant polycystic kidney disease, ended when development stopped (registry record read September 30, 2026).
  7. [pubmed] Dahl E, et al. "Meta-analysis: the safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatraemia." Aliment Pharmacol Ther, 2012;36(7):619-26. PMID: 22908905.

Sources & Citations

Every study here was read from its PubMed record. The discontinuation comes from Centessa's June 2, 2022 SEC filing.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.

Last reviewed: 2026-09-30