Targeting the Right Ventricle in Pulmonary Hypertension

Inclusion Criteria:

- Symptomatic pulmonary hypertension based on one of the following criteria: Idiopathic
pulmonary arterial hypertension, Familial pulmonary arterial hypertension, pulmonary
hypertension associated with connective tissue disease, chronic thromboembolic
pulmonary hypertension-nonsurgical/distal vessel disease or patients who are reluctant
to go to surgery within a 6-month period and are willing to participate, simple
congenital such as repaired atrial septal defect or ventricular septal defect or
unrepaired small atrial septal defect or ventricular septal defect with persistent and
out of proportion pulmonary arterial hypertension, group 3 patients who have a
component of pulmonary arterial hypertension, pulmonary arterial hypertension caused
by conditions affect the veins and small vessels of the lungs, sickle cell disease,
group 5 pulmonary hypertension such as polycythemia vera, essential thrombocythemia,
sarcoidosis, or vasculitis, or metabolic disorder.

- WHO functional class II, III, or IV

- Mean pulmonary artery pressure >25 mmHg at rest

- Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15
mmHg

- Baseline 6-minute walk test distance > 50 meters

- Stable on baseline existing PH specific therapy for 12 weeks with no dosage change
within 28 days prior to screening.

Exclusion Criteria:

- Previous treatment with or prior sensitivity to ranolazine

- Any family history of corrected QT interval prolongation, congenital long QT syndrome,
or receiving drugs that prolong the corrected QT interval

- Parenchymal lung disease showing total lung capacity < 50% of predicted OR forced
expiratory volume at one second/forced vital capacity < 50%

- Portal hypertension associated with liver disease

- Left sided heart disease including any of the following: moderate or greater aortic or
mitral valve disease, Any left ventricle cardiomyopathy, Left ventricular systolic
dysfunction defined as an ejection fraction < 50%, Symptomatic coronary artery disease

- Uncontrolled hypertension

- Uncontrolled diabetes