Purpose

This is a multicenter, randomized (1:1; oral treprostinil to placebo), double-blind, placebo-controlled study in subjects with World Health Organization (WHO) Group 2 pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). Once randomized, subjects will take the initial dose of study drug at the study site on the day of randomization. Subjects will return to the study site for visits scheduled at Weeks 6, 12, 18, and 24. The treatment phase of the study will last approximately 24 weeks.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. A subject can qualify if they have undergone a right heart catheterization (RHC) within 180 days of Baseline.
  2. The subject has a diagnosis of heart failure with a left ventricular ejection fraction (LVEF) ≥45% by echocardiogram (ECHO) completed during Screening (prior to randomization).
  3. The subject's baseline 6MWD must be at least 150 meters.
  4. The subject has pulmonary function tests conducted within 6 months of Screening or during the Screening phase.
  5. Subjects on a chronic medication for heart failure must be on a stable dose for ≥30 days prior to randomization.
  6. Subjects on chronic medications for any underlying respiratory condition must be on a stable dose for ≥30 days prior to randomization.

Exclusion Criteria

  1. The subject is pregnant or lactating.
  2. In the opinion of the Principal Investigator, the subject has a primary diagnosis of PH other than WHO Group 2 PH.
  3. The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation of therapy or inability to effectively titrate that therapy.
  4. The subject has received any approved PAH therapies within 30 days of randomization. Chronic use of an approved phosphodiesterase type 5 inhibitor (PDE5-I) is allowed as long as the subject has been on a stable dose for at least 90 days prior to randomization and has had an RHC confirming the parameters necessary for inclusion in the study after being on a stable PDE5-I dose for at least 30 days.
  5. The subject has been hospitalized for a cardiopulmonary indication within 30 days of randomization.
  6. The subject had a myocardial infarction within 90 days of randomization.
  7. The subject had cardiac resynchronization therapy within 90 days of randomization or anticipated resynchronization therapy during the study treatment period.
  8. The subject has liver function tests greater than 3 times the upper limit of normal at Screening, clinically significant liver disease/dysfunction, known Child-Pugh Class C hepatic disease, or noncirrhotic portal hypertension.
  9. The subject has uncontrolled systemic hypertension, systolic blood pressure <100 mmHg, or a resting heart rate >100 beats per minute at Baseline.
  10. The subject has known genetic hypertrophic cardiomyopathy, sarcoidosis, or cardiac amyloidosis.
  11. The subject has a known history of any LVEF less than 40% by ECHO within 3 years of randomization. Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition (eg, atrial fibrillation) is allowed.
  12. The subject has hemodynamically significant valvular heart disease as determined by the Investigator, including: greater than mild aortic and/or mitral stenosis or severe mitral and/or aortic regurgitation (>Grade 3)
  13. The subject has a Body Mass Index >45 kg/m^2.
  14. The subject has any musculoskeletal disorder, or has any other condition that limits ambulation.
  15. The subject has end-stage renal disease requiring/receiving dialysis.
  16. The subject participated in an investigational drug or device study within 30 days prior to signing consent.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Oral treprostinil
Sustained-release oral tablets for three times daily (TID) administration
  • Drug: Oral treprostinil
    Sustained-release oral tablets for TID administration
    Other names:
    • Treprostinil diethanolamine
Placebo Comparator
Placebo
Placebo (sugar pill) for TID oral administration
  • Drug: Placebo
    Placebo (sugar pill) for TID oral administration
    Other names:
    • Matching placebo (sugar pill)

More Details

NCT ID
NCT03037580
Status
Active, not recruiting
Sponsor
United Therapeutics

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.