Levosimendan in Pulmonary Hypertension Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy of TNX-103 (levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to Week 12).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a Phase 3, double-blind, randomized, placebo-controlled study of levosimendan in patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will provide written informed consent prior to completing any study procedures. Upon meeting all eligibility criteria, patients will continue to the 12-week randomized, double-blind treatment phase. Approximately 152 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan or placebo 2 mg/day for Weeks 1 to 4 and 3 mg/day for Weeks 5 to 12. Subjects will return to the clinical site at Weeks 4, 8, and 12.
All randomized subjects will have the option to enter the 92-week OLE following the completion of all study events at Week 12.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Placebo
|
| Active Comparator: TNX-103 levosimendan |
Drug: TNX-103
levosimendan 1 mg
|
Outcome Measures
Primary Outcome Measures
- Six-minute walk distance from Baseline to Week 12 [12 weeks]
Secondary Outcome Measures
- KCCQ [12 weeks]
- Clinical Worsening Events [12 weeks]
- NT-proBNP [12 weeks]
- NYHA functional class [12 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men or women, greater than or equal to18 to 85 years of age.
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NYHA Class II or III or ambulatory NYHA class IV symptoms.
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A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics
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A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC done prior to study consent.
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A qualifying echocardiogram performed within 30 days showing an LVEF greater than or equal to 40%
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A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening
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A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish the resting heart rate (HR) and rhythm.
-
Chronic medications for heart failure with preserved ejection fraction (HFpEF) or other serious underlying cardiac or pulmonary conditions should be administered at a stable dose for greater than or equal to 30 days prior to the day of the Baseline 6-MWT.
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Female subjects of childbearing potential must have a negative urine pregnancy test result at the Screening Visit and a negative urine pregnancy test and must not be pregnant, lactating, or planning a pregnancy from the Screening Visit to 7 months after the last dose of study drug.
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Female subjects of childbearing potential will be included if they are either sexually inactive (abstinent) for 90 days prior to the first dose of study drug, or are using a highly effective birth control method
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Female subjects of nonchildbearing potential will be included if they meet the following definition of nonchildbearing potential: are either surgically sterile or postmenopausal.
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Male patients with female partners of childbearing potential must use highly effective methods of birth control during their participation in the study and for a period of 4 months after the last dose of study drug.
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Patients must agree to abstain from egg or sperm donation through 7 months for female patients and 4 months for male patients after administration of the last dose of study drug.
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Ability to adhere to study visit schedule and understand and comply with all protocol requirements.
-
Signed informed consent document indicating that they understand the purpose and procedures required for the study and are willing to participate in the study.
Exclusion Criteria:
-
A diagnosis of PH WHO Groups 1, 3, 4, or 5.
-
Walking activity that is limited by anything other than shortness of breath or fatigue attributed to PH-HFpEF.
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Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
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Structural heart repair or replacement of the aortic valve or mitral valve (surgical or percutaneous) within the past 12 months. OR, planned valve intervention in the next 6 months. OR, the presence of echocardiographic findings of significant valve disease as assessed from the qualifying echocardiogram
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Any of the following clinical laboratory values within 30 days as specified:
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Hemoglobin <10 g/dL per local laboratory.
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Serum alanine aminotransferase or aspartate aminotransferase levels >3× upper limit of normal (ULN) or total bilirubin >3× ULN.
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Electrocardiogram (ECG) with a QTcF >450 msec for males and >470 msec for females at Screening and Baseline in the absence of right bundle branch block.
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Platelet count <75,000/mm3.
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A diagnosis of pre-existing lung disease
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Recent documentation of significant underlying lung disease
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Documentation of pulmonary thromboembolism in the last 12 months
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Cardiovascular co-morbidities
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Receipt of any approved pulmonary arterial hypertension-specific therapies
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Hospitalization for any indication within 30 days
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Receipt of any intravenous (IV) inotropes within 30 days
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Body mass index greater than or equal to 50 kg/m2.
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Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
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Known history of chronic liver disease
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Prior exposure to levosimendan
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Current enrollment in or completion of any other investigational product study within 30 days of Screening.
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Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days
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History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product.
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Major surgery within 60 days. Subjects must have completely recovered from any previous surgery.
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Prior heart, lung, or heart-lung transplants or life expectancy of <12 months
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Pregnancy or breastfeeding in females
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History of active malignancy, with the exception of fully treated basal cell carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin.
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History of clinically significant other diseases that may limit or complicate participation in the study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Tenax Therapeutics, Inc.
- Medpace, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TNX-103-06