Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication

The purpose of this study is to assess tolerability and clinical effects of transition from
intravenous (IV, needle in the vein) or subcutaneous (SQ, needle in the skin) to the
recently-approved inhaled treprostinil (Tyvaso) for the treatment of pulmonary arterial
hypertension (PAH).

Our hypothesis is that the transition to inhaled treprostinil will be tolerated by patients.

The intravenous and subcutaneous drugs epoprostenol and treprostinil received approval for
treatment of PAH many years ago. While these medications improve exercise capacity and the
symptoms of PAH, they are given by injection and thus have several side effects, such as pain
and catheter infection. This has resulted in many patients either refusing to take the
medication or quitting these medications because of not tolerating them.

The only other form of prostacyclin treatment available for PAH patients is inhaled. There
are 2 inhaled prostacyclins approved for PAH, however one of these requires at least 6
inhalations per day, every day, and takes about 30 minutes to inhale each time. Thus, it has
not been a regularly-used medication and issues surrounding compliance make it a riskier drug
to use if patients do not get their full doses every day. The other inhaled medication,
treprostinil, was approved a few months ago, only needs to be given 4 times a day, and takes
about 2-3 minutes to inhale.

Since inhaled treprostinil can be administered easily, it is anticipated that many patients
will transition from epoprostenol or treprostinil to the recently approved inhaled
treprostinil, however we do not know if this is a safe or effective way to manage patients.
Thus, the goal of this prospective study is to gather observational data regarding how that
switch is made, tolerability of the switch, and, to the extent possible with this
methodology, assess clinical effects of the switch.

This is a prospective study. Twenty patients > 18 years old with PAH will be enrolled.
Patients enrolled will be those in whom a clinical decision to convert from either IV
epoprostenol, IV treprostinil, or SQ treprostinil to inhaled treprostinil therapy has been
made. This is usually the result of patients asking to switch to inhaled therapy, but only
allowed by physicians if they feel the switch would be safe.

If eligible, and after informed consent, patients will have a history and physical
examination, a 6 min walk test, a cardiopulmonary exercise test (CPET), blood tests, and a
symptom questionnaire will be filled out. Patients will then be admitted to the hospital
where a monitoring catheter will be placed inside the patient's heart and inhaled
treprostinil will be initiated, while the dose of IV/SQ medication is reduced over about
24-26 hours.

Clinical follow-up will be at weeks 1, 4, and 12.

The procedures above are all part of the routine clinical care that patients would receive if
they were to be transitioned to inhaled therapy, including the hospitalization and
catheterization. The criteria for them to be able to be switched are conservative. Pressure
in their heart and lungs must be low (mPAP < 40 mmHg and RAP <12 mmHg on catheterization),
and their dose of IV or SQ medication must be low (< 20 ng/kg/min). Regarding the patient
subset enrolled in this study in whom a clinical decision to convert transition therapy has
been made, we will try to ensure that our clinical decision-making will not be influenced by
the need to enroll subjects in the study by explicitly noting the potential for conflict of
interest with each patient (addressed in the ICF). We will not make a clinical decision for
our patients based on the desire to fill the study numbers, and every will be made to avoid
the potential for a perceived conflict of interest.