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Levosimendan (TNX-103)

Phase 3

Coronary Artery Bypass Grafting | Small molecule | Cardiovascular |Tenax Therapeutics, Inc.|Last Updated: Sep 9, 2026

Target and mechanism

Molecular targetPDE3A, PDE3B, TNNC1, TNNI3, TNNT2
Target classInhibitor
ModalitySmall molecule

Also known as TNX-103, Levosimendan

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment882

FDA Designations

No designations recorded

Clinical trial landscape

Levosimendan (TNX-103) · 6 trials · 10 indications

Phase 3 4Phase 2 2
NCT07436689Long-Term Open-Label Extension Study of Oral LevosimendanPulmonary Hypertension Associated With HFpEF
ENROLLING BY_INVITATION800 Analytics
NCT07288398LEVEL-2: LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF-2Pulmonary Hypertension Associated With HFpEF
RECRUITING540 Analytics
NCT05983250LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEFPulmonary Hypertension
ACTIVE NOT_RECRUITING230 Analytics
NCT02025621Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary BypassCoronary Artery Bypass Grafting
COMPLETED882 Analytics
PHASE3ENROLLING BY_INVITATION
Long-Term Open-Label Extension Study of Oral Levosimendan
Pulmonary Hypertension Associated With HFpEFUnlock trial analytics
PHASE3RECRUITING
LEVEL-2: LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF-2
Pulmonary Hypertension Associated With HFpEFUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF
Pulmonary HypertensionUnlock trial analytics
PHASE3COMPLETED
Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
Coronary Artery Bypass GraftingUnlock trial analytics

Study Endpoints

Primary Endpoints

The incidence (i.e., the percentage of patients who experience at least 1 occurrence) of select AE/SAEs
From enrollment through study completion (up to 3 years)

The incidence (i.e., the percentage of patients who experience at least 1 occurrence) of select AE/SAEs will be tabulated by system organ class and preferred term.

6-Minute Walk Distance (6MWD)
26 weeks

Change in 6-minute walk distance

Change in Six-minute walk distance
12 weeks
Number of Dual Efficacy Endpoint Events
30 days

The all-cause death at 30 days or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) through Day 5

Number of Quad Efficacy Endpoint Events
30 days

Composite of all-cause death (at 30 days), or perioperative nonfatal MI \[CK-MB \>10xULN or \>100 ng/mL, CK-MB \>5xULN or 50 ng/mL with new Q wave (\>0.04 seconds wide in two contiguous leads) or new left bundle branch block)\] (through Day 5), or need for renal dialysis (through Day 30), or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) (through Day 5)

Clinical Safety
Duration of study (for up to 2 years); Assessed at Weeks 3, 6, 12, 24, and 48 and Follow-Up Visit (termination visit).

Number of Adverse Events per Patient Population

Change From Baseline Pulmonary Capillary Wedge Pressure (PCWP) With Bicycle Exercise
Baseline, Week 6

Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise at Week 6

Secondary Endpoints

KCCQ (Kansas City Cardiomyopathy Questionnaire) score is a standardized measure that ranges from 0 to 100, where a higher score indicates better health.
26 weeks
Clinical Worsening Events
26 weeks
Clinical Worsening Event
26 weeks
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TNX-103EXPERIMENTALOpen-label oral levosimendan 1-3mg
PlaceboPLACEBO_COMPARATORMatching placebo (oral)
LevosimendanEXPERIMENTALlevosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan Open-LabelOTHERInitial: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion. Ongoing patients are transitioned to daily oral levosimendan (1mg capsules TID)
Levosimendan 2.5mg/mL Injectable SolutionEXPERIMENTAL0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Matching PlaceboPLACEBO_COMPARATOR0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Interventions

NameTypeDescription
TNX-103DRUGOpen-label oral levosimendan 1-3mg
PlaceboDRUGMatching placebo (oral)
LevosimendanDRUG -
Matching PlaceboDRUGA sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion
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Eligibility Criteria

Age Range18 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites9

Inclusion Criteria: * Completed a TNX-103 parent study * Investigator confirmation that participant may derive clinical benefit from continued access to TNX-103 * Requirements related to childbearing potential, contraception, and egg/sperm donation Exclusion Criteria: * Investigator or Sponsor op...

Countries:United StatesArgentinaAustriaBrazilBulgariaCzechiaFranceGermanyHungaryItalyPolandSouth KoreaSpainTaiwanUnited KingdomCanada
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Recent Changes (Last 90 Days)

LOWSep 9, 2026NCT07436689lastUpdatePostDate: changed
LOWSep 9, 2026NCT07436689lastUpdatePostDate: changed
LOWAug 20, 2026NCT07288398lastUpdatePostDate: changed
LOWAug 20, 2026NCT07288398lastUpdatePostDate: changed
LOWAug 20, 2026NCT07288398lastUpdatePostDate: changed
LOWAug 20, 2026NCT07288398lastUpdatePostDate: changed
LOWJul 24, 2026NCT05983250primaryCompletionDate: changed
LOWJul 24, 2026NCT05983250primaryCompletionDate: changed
MEDIUMJul 21, 2026NCT05983250Status: RECRUITING → ACTIVE_NOT_RECRUITING
LOWJul 20, 2026NCT07436689lastUpdatePostDate: changed
LOWJul 20, 2026NCT07436689lastUpdatePostDate: changed

Frequently asked questions about Levosimendan (TNX-103)

What is levosimendan (TNX-103) used for?

Levosimendan (TNX-103) is being developed for pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF), as well as pulmonary hypertension and coronary artery bypass grafting. It is an investigational small molecule in Phase 3 development and has not been approved by the FDA.

What does levosimendan (TNX-103) target?

Levosimendan (TNX-103) targets PDE3A and PDE3B as an inhibitor, and also binds cardiac troponin components TNNC1, TNNI3, and TNNT2. This dual mechanism combines phosphodiesterase inhibition with calcium sensitization of the cardiac contractile apparatus, supporting its development in cardiovascular and pulmonary hypertension indications.

Who is developing levosimendan (TNX-103)?

Tenax Therapeutics, Inc. (ticker: TENX) is developing levosimendan under the designation TNX-103. The company is running Phase 3 clinical programs for the asset in pulmonary hypertension associated with HFpEF, with trials enrolling across the United States and multiple international sites.

What phase is levosimendan (TNX-103) in?

Levosimendan (TNX-103) is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. The Phase 3 program includes the LEVEL-2 trial and a long-term open-label extension study, with earlier Phase 2 work completed in PH-HFpEF patients.

What clinical trials is levosimendan (TNX-103) in?

Levosimendan (TNX-103) is being studied in several trials, including NCT07288398 (LEVEL-2, Phase 3, recruiting), NCT07436689 (Phase 3 long-term open-label extension, enrolling by invitation), NCT05983250 (Phase 3, active not recruiting), and the completed Phase 2 rollover study NCT03624010. Total enrollment across these studies is approximately 1,340 patients.

Is TNX-103 the same as levosimendan?

Yes, TNX-103 is the development designation used by Tenax Therapeutics for levosimendan. The two names refer to the same small molecule asset, so searches for either TNX-103 or levosimendan point to the same Phase 3 pulmonary hypertension program in PH-HFpEF.