A Single-arm Open Label Study Evaluating the Impact on Lifestyle of a New Thermo-stable Formulation of Flolan in Subjects with Pulmonary Arterial Hypertension (PAH) (FLR115332)

Flolan (epoprostenol sodium) for injection is a sterile sodium salt formulated
for intravenous (IV) administration. Epoprostenol (also called PGI2, PGX,
prostacyclin) is a naturally occurring prostaglandin with potent vasodilatory
activity and inhibitory activity of platelet aggregation. Epoprostenol has two
major pharmacological actions 1) direct vasodilatation of pulmonary and
systemic arterial vascular beds, and 2) inhibition of platelet aggregation.
Flolan is an effective treatment for pulmonary arterial hypertension. It is
administered in a portable continuous infusion in ambulant patients. However,
safe and effective administration is complex and requires a considerable level
of commitment from patients. The current marketed formulation of Flolan
requires reconstitution and dilution every two days and the reconstituted
solution may only be administered up to 24 hours when it is maintained between
a temperature of 2° and 8°C (36° to 46° F) during infusion, thereby,
necessitating the use of a cold pack. In addition, the cold pack used to
maintain the temperature of the reconstituted solution must be changed every 12
hours.
GSK is currently developing a new formulation of FLOLAN diluent, which is more
stable at ambient temperatures. No change will be made to the vial that
contains the lyophilised epoprostenol. The only change will be the pH of the
diluent. It is not expected to have any impact on the pharmacodynamic actions.
The new formulation may be reconstituted and diluted every 6 days and is stable
for 24 hours up to 35°C (95° F) and for 48 hours up to 25°C (77° F); it does
not, therefore, require the use of a cold pack or frequent changes of the
cassette. In this way, it is anticipated that the new formulation will provide
an added level of convenience to patients.
The primary purpose of this study is to demonstrate that the new formulation of
Flolan will result in greater convenience and ease of administration thereby
improving quality of life for those patients transitioning from the old
formulation to the new thermo stable formulation.

Primary:
* To describe the effect of the new thermo stable formulation of FLOLAN on
quality of life in patients switching from the currently marketed FLOLAN to the
new thermo stable formulation.
* To determine the dose titration requirement
Secondary:
* Safety and tolerability.
* Efficacy.
Exploratory:
* Hemodynamic parameters in a subset of subjects.

Multicenter open label non-randomized non-comparative phase IV study. Run-in
period 4 weeks with old formulation. Treatment period approx. 4 weeks with new
formulation. Optional extension phase until new formulation is commercially
available.
Approx. 20 patients, thereof 5 in NL.

Treatment with the new Flolan formulation.

Risk: Adverse effects of study medication.
Burden: Study duration 9-11 weeks. 3 visits, 2 phone calls. Duration visits 3-8
h (observation period after start study medication may be extended from 6 to 48
h if needed).
Physical examination 3 times.
Blood tests 3 times, 10-20 ml/occasion.
Optional pharmacogenetic/-genomics blood test (10 ml).
Pregnancy test (if relevant) 3 times.
ECG 3 times.
Non-invasive oxygen saturation 3 times.
6 min walk test 3 times.
Questionnaires (2) 2 times.
Option to enter extension period (until new formulation is commercially
available):
Every 3 months alternating visit and phone call.
Every 6 months: blood tests, 10-20 ml/occasion, pregnancy test (if relevant),
oxygen saturation.