Study of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat Pulmonary Arterial Hypertension (PAH)

This is a multicentre, open label, single-arm study in approximately 20 adult patients (18 -
75 years old) designed to evaluate the Impact on lifestyle of a new thermo stable formulation
of epoprostenol sodium in subjects with Pulmonary Arterial Hypertension (PAH). The co-primary
objectives are 1) to describe the effect of the new thermo stable formulation of epoprostenol
sodium on quality of life and 2) to determine the dose titration requirement in patients
switching from the currently marketed FLOLAN (epoprostenol sodium) to the new thermo stable
formulation. Secondary objectives include assessing the safety, tolerability and efficacy of
the thermo stable formulation of epoprostenol sodium and the exploratory objective is to
evaluate the effect of the new thermo stable formulation of epoprostenol sodium on
haemodynamic parameters in a subset of subjects.

Subjects who are already receiving FLOLAN (epoprostenol sodium) for the treatment of PAH and
have been on a stable dose for at least 3 months and on stable doses of other PAH treatments
for at least 30 days prior to screening will be enrolled. After a screening visit, eligible
subjects will have a 4-week run-in period with their existing FLOLAN (epoprostenol sodium)
treatment. At the end of the 4-week period, they will be admitted to the clinic for baseline
assessments and for switching to study medication (the new thermo stable formulation of
epoprostenol sodium). Subjects will remain in hospital for a minimum of 6 hours to ensure
clinical and hemodynamic stability prior to discharge. Subjects may stay in hospital for up
to 24-48 hours after switching to the new thermo stable formulation of epoprostenol sodium at
the discretion of the investigator. Dose titration requirement will be assessed at the time
of discharge. Haemodynamic parameters will be obtained in a subgroup of subjects enrolled in
centres where the collection of haemodynamic data is considered part of the standard of care.
Subjects will receive the study medication as a continuous intravenous infusion for a 4-week
treatment period. Those who complete the 4-week treatment period will have the option of
entering an extension phase of the study to continue receiving the new formulation.

Inclusion Criteria:

- Adult male or female at least 18 to 75 years at the time of screening.

- Subjects must have been on FLOLAN (epoprostenol sodium) therapy for pulmonary arterial
hypertension (PAH) as approved in the product label.

- Subjects must be on stable doses of their existing FLOLAN (epoprostenol sodium)
treatment for a minimum of 3 months prior to screening.

- Subjects must be on stable doses of any current PAH treatments other than FLOLAN
(epoprostenol sodium) in the last 30 days.

- Subjects must walk a distance of at least 150 meters during six-minute walk distance
test (6MWD). This test must be completed during the Screening Visit.

- A female subject is eligible to participate if she is of non-childbearing potential or
of childbearing potential, has a negative pregnancy test at screen, and agrees to use
one of the contraception methods listed in the protocol.

- Subjects must be competent to understand the information given in the Institutional
Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent
form and must sign the form prior to the initiation of any study procedures.

Exclusion Criteria:

- Subjects who are given FLOLAN (epoprostenol sodium) for a condition or in a manner
that is outside the approved indication.

- Subjects with congestive heart failure arising from severe left ventricular
dysfunction.

- Subjects, with or without supplemental oxygen, who have a resting arterial oxygen
saturation (SaO2) <90% as measured by pulse oximetry at screening.

- Subjects have been hospitalized as an emergency or visited the emergency room for a
condition related to PAH or treatment for PAH in the last 3 months.

- The subject's clinical condition is such that they are not expected to remain
clinically stable for the duration of the study.

- Female subjects who are pregnant or breastfeeding.

- Subjects who have demonstrated noncompliance with previous medical regimens.

- Subjects who have a history of abusing alcohol or illicit drugs within 1 year.

- Subjects with a diagnosis of active hepatitis (hepatitis B surface antibody and
hepatitis C antibody).

- Subjects who have participated in a clinical study involving another investigational
drug or device within four weeks before screening.

- Subjects who had history malignancies within the past 5 years, with the exception of
basal cell carcinoma of the skin or in situ carcinoma of the cervix.

- Any concurrent condition that would affect the safety of the subject or in the opinion
of the investigator it is not in the best interest of the patient to participate in
the study.