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

Condition(s) targeted: Hypertension, Pulmonary

Intervention: current marketed FLOLAN (epoprostenol sodium) (Drug); new thermo stable formulation of epoprostenol sodium (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

The purpose of this multicentre, open label, single-arm study in approximately 20 adult patients is to evaluate the Impact on lifestyle of a new thermo stable formulation of epoprostenol sodium in subjects with Pulmonary Arterial Hypertension (PAH).

Official title: 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). (FLOLAN® is a Registered Trademark of the GlaxoSmithKline Group of Companies.)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Quality of life assessment

Time required to prepare medication and effect of treatment on daily activities

change from baseline in dose of thermo stable epoprostenol sodium

Secondary outcome:

safety and tolerability (number of subjects with adverse events, infusion site reactions and haematology and clinical chemistry parameters outside the normal range, change from baseline in vital signs).

efficacy (change from baseline in 6-minute walk distance, breathlessness after the 6MWD - Borg Dyspnoea Index and WHO functional class).

Detailed description:

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

GSK Investigational Site, Quebec G1V 4G5, Canada

GSK Investigational Site, Amsterdam 1081 HV, Netherlands

GSK Investigational Site, Miami Beach, Florida 33140, United States

GSK Investigational Site, Chicago, Illinois 60637, United States

GSK Investigational Site, Baltimore, Maryland 21205, United States

GSK Investigational Site, Boston, Massachusetts 02118-2393, United States

GSK Investigational Site, Columbus, Ohio 43221, United States

GSK Investigational Site, Dallas, Texas 75390-8550, United States

Starting date: November 2011
Last updated: May 15, 2014