Clinical trial NCT01462565: Study of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension, Pulmonary
Keywords: flolan
pulmonary arterial hypertension
thermo stable formulation
epoprostenol sodium
modified sterile diluent
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-31
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3)
measure: Change From Baseline in Study Specific Participant Acceptance Survey
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3).
measure: Change From Baseline in Dose of Thermo Stable Epoprostenol Sodium at Week 4
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Secondary outcomes:
measure: Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs)
timeFrame: Up to visit 3 (Week 4)
measure: Number of Participants With Infusion Site Reactions During Treatment Period
timeFrame: Baseline visit (Visit 2) to Week 4 (Visit 3)
measure: Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4(Visit 3)
measure: Change From Baseline in Vital Signs at Week 4: Heart Rate
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
measure: Number of Participants With Abnormal Clinical Chemistry
timeFrame: Up to 1 week after Week 4 (Follow-up)
measure: Number of Participants With Abnormal Hematology
timeFrame: Up to 1 week after Week 4 (Follow-up)
measure: Number of Participants With Abnormal Urinalysis
timeFrame: Up to 1 week after Week 4 (Follow-up)
measure: Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
measure: Breathlessness After 6MWD - Borg Dyspnoea Index (BDI)
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
measure: World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment
timeFrame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
measure: Mean Oxygen Saturation in Blood Over Time
timeFrame: up to the treatment follow up (1 week after Visit 3 [Week 4])
measure: Number of Participants With Urine Pregnancy Test Positive
timeFrame: up to the treatment follow up (1 week after Visit 3 [Week 4])
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Provencher S, Paruchuru P, Spezzi A, Waterhouse B, Gomberg-Maitland M; pH12 Flolan reformulation study group. Quality of life, safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension. PLoS One. 2015 Mar 20;10(3):e0120657. doi: 10.1371/journal.pone.0120657. eCollection 2015.