Back to resultsStudy of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat Pulmonary Arterial Hypertension (PAH)
Primary Purpose
Hypertension, Pulmonary
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
current marketed FLOLAN (epoprostenol sodium)
new thermo stable formulation of epoprostenol sodium
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring flolan, pulmonary arterial hypertension, thermo stable formulation, epoprostenol sodium, modified sterile diluent
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All subjects
Arm Description
Subjects enter the study already taking current marketed FLOLAN (epoprostenol sodium) and continue for 4 weeks (run-in). At baseline, they will be swopped to the new thermo stable formulation of epoprostenol sodium for 4 weeks (or longer if they continue in the extension phase of the study).
Outcomes
Primary Outcome Measures
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)
Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Subscale and summary scores range: 0-100. Higher subscale and summary scores was considered as better health status. Change from Baseline was calculated as score at observation minus score at baseline. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).
Change From Baseline in Study Specific Participant Acceptance Survey
Study-specific questionnaire comprised the pre-defined15 questions which included activities of daily living assessment. Participants rated the question on a scale of 1 to 10, where 1 was do not agree and 10 was strongly agree. Change from Baseline was calculated as score at observation minus score at Baseline. Changes from Baseline was assessed for Questions 2 to 12. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).
Change From Baseline in Dose of Thermo Stable Epoprostenol Sodium at Week 4
Dose titration requirement was assessed at the time of discharge. Change from Baseline was calculated as score at observation minus score at Baseline. Units- nanogram per kilogram per minute (ng/kg/min). Baseline was Visit 2 i.e . Day-14 (+ or - 7 days).
Secondary Outcome Measures
Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs)
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, congenital anomaly/birth defect and medically significant and all events of possible drug-induced liver injury with hyperbilirubinaemia. Only treatment emergent AEs and SAEs were reported in this outcome measure. Specifically, this study reported 2 SAEs, but only 1 was categorized as treatment emergent.
Number of Participants With Infusion Site Reactions During Treatment Period
Infusion site reactions were reported during the treatment period. Infusion site was inspected for erythema, excoriation, induration, skin necrosis or signs of local sepsis.
Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure
Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).
Change From Baseline in Vital Signs at Week 4: Heart Rate
Summary mean change in heart rate measured in beats per minute (beats/min or BPM). Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).
Number of Participants With Abnormal Clinical Chemistry
Abnormal clinical chemistry was analyzed as follows: serum alanine aminotransferase (ALT/SGPT) >= 3 x upper limit of normal (ULN) , aspartate aminotransferase (AST/SGOT) >= 3 x ULN , total bilirubin >= 34.2, creatinine >= 176.8.
Number of Participants With Abnormal Hematology
Values for hemoglobin, hematocrit, and platelet count were analyzed. Participants with abnormal values have been reported. The low and high value concern were as follows: hemoglobin (Males < 98, >180.0) (females <91, >161.0)grams per litre (g/L); hematocrit (Males < 32.0, >54.0) (females <29.0, >50.6) fraction (1); platelet count (< 100, > 500) gram international units per litre (gI/L).
Number of Participants With Abnormal Urinalysis
Dipstick method was used to measure blood, glucose and protein. Data was analyzed up to 1 week after Week 4 (Follow-up visit).
Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment
This assessment was a non-encouraged test that measures the distance walked for a duration of 6 minutes. Change from Baseline was calculated as value at observation minus value at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).
Breathlessness After 6MWD - Borg Dyspnoea Index (BDI)
The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. The BDI scale was assessed by each participant. Change from Baseline = score at observation minus score at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).
World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment
World Health Organization functional class was analyzed as class I, class II, class III and class IV. World Health Organization functional class was analyzed at Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4. The classed were defined as Class I: No symptoms of pulmonary arterial hypertension with exercise or at rest, Class II: No symptoms at rest but uncomfortable and short of breath with normal activity, Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting and Class IV: Symptoms at rest and severe symptoms with any activity. Hence the severity increased from class I (better) to Class IV (worse).
Mean Oxygen Saturation in Blood Over Time
Pulse oximetry (oxygen saturation) was analyzed. Data for Pulse oximetry (oxygen saturation) was analyzed up to the treatment follow up (1 week after Visit 3 [Week 4]).
Number of Participants With Urine Pregnancy Test Positive
Urine samples were collected for urine pregnancy test. Urine samples were collected at up to the treatment follow up (1 week after Visit 3 [Week 4]). Number of participants with urine pregnancy test positive has been reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01462565
Brief Title
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
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
November 1, 2011 (undefined)
Primary Completion Date
May 16, 2012 (Actual)
Study Completion Date
November 8, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
flolan, pulmonary arterial hypertension, thermo stable formulation, epoprostenol sodium, modified sterile diluent
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All subjects
Arm Type
Experimental
Arm Description
Subjects enter the study already taking current marketed FLOLAN (epoprostenol sodium) and continue for 4 weeks (run-in). At baseline, they will be swopped to the new thermo stable formulation of epoprostenol sodium for 4 weeks (or longer if they continue in the extension phase of the study).
Intervention Type
Drug
Intervention Name(s)
current marketed FLOLAN (epoprostenol sodium)
Intervention Description
continuous intravenous infusion
Intervention Type
Drug
Intervention Name(s)
new thermo stable formulation of epoprostenol sodium
Intervention Description
continuous intravenous infusion
Primary Outcome Measure Information:
Title
Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)
Description
Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Subscale and summary scores range: 0-100. Higher subscale and summary scores was considered as better health status. Change from Baseline was calculated as score at observation minus score at baseline. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3)
Title
Change From Baseline in Study Specific Participant Acceptance Survey
Description
Study-specific questionnaire comprised the pre-defined15 questions which included activities of daily living assessment. Participants rated the question on a scale of 1 to 10, where 1 was do not agree and 10 was strongly agree. Change from Baseline was calculated as score at observation minus score at Baseline. Changes from Baseline was assessed for Questions 2 to 12. Baseline was defined as Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3).
Title
Change From Baseline in Dose of Thermo Stable Epoprostenol Sodium at Week 4
Description
Dose titration requirement was assessed at the time of discharge. Change from Baseline was calculated as score at observation minus score at Baseline. Units- nanogram per kilogram per minute (ng/kg/min). Baseline was Visit 2 i.e . Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Secondary Outcome Measure Information:
Title
Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs)
Description
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, congenital anomaly/birth defect and medically significant and all events of possible drug-induced liver injury with hyperbilirubinaemia. Only treatment emergent AEs and SAEs were reported in this outcome measure. Specifically, this study reported 2 SAEs, but only 1 was categorized as treatment emergent.
Time Frame
Up to visit 3 (Week 4)
Title
Number of Participants With Infusion Site Reactions During Treatment Period
Description
Infusion site reactions were reported during the treatment period. Infusion site was inspected for erythema, excoriation, induration, skin necrosis or signs of local sepsis.
Time Frame
Baseline visit (Visit 2) to Week 4 (Visit 3)
Title
Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure
Description
Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4(Visit 3)
Title
Change From Baseline in Vital Signs at Week 4: Heart Rate
Description
Summary mean change in heart rate measured in beats per minute (beats/min or BPM). Change from Baseline was calculated as the value at the indicated time points minus the value at Baseline. Baseline was Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
Title
Number of Participants With Abnormal Clinical Chemistry
Description
Abnormal clinical chemistry was analyzed as follows: serum alanine aminotransferase (ALT/SGPT) >= 3 x upper limit of normal (ULN) , aspartate aminotransferase (AST/SGOT) >= 3 x ULN , total bilirubin >= 34.2, creatinine >= 176.8.
Time Frame
Up to 1 week after Week 4 (Follow-up)
Title
Number of Participants With Abnormal Hematology
Description
Values for hemoglobin, hematocrit, and platelet count were analyzed. Participants with abnormal values have been reported. The low and high value concern were as follows: hemoglobin (Males < 98, >180.0) (females <91, >161.0)grams per litre (g/L); hematocrit (Males < 32.0, >54.0) (females <29.0, >50.6) fraction (1); platelet count (< 100, > 500) gram international units per litre (gI/L).
Time Frame
Up to 1 week after Week 4 (Follow-up)
Title
Number of Participants With Abnormal Urinalysis
Description
Dipstick method was used to measure blood, glucose and protein. Data was analyzed up to 1 week after Week 4 (Follow-up visit).
Time Frame
Up to 1 week after Week 4 (Follow-up)
Title
Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment
Description
This assessment was a non-encouraged test that measures the distance walked for a duration of 6 minutes. Change from Baseline was calculated as value at observation minus value at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Title
Breathlessness After 6MWD - Borg Dyspnoea Index (BDI)
Description
The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. The BDI scale was assessed by each participant. Change from Baseline = score at observation minus score at Baseline. Baseline visit was Visit 2 i.e. Day-14 (+ or - 7 days).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
Title
World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment
Description
World Health Organization functional class was analyzed as class I, class II, class III and class IV. World Health Organization functional class was analyzed at Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4. The classed were defined as Class I: No symptoms of pulmonary arterial hypertension with exercise or at rest, Class II: No symptoms at rest but uncomfortable and short of breath with normal activity, Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting and Class IV: Symptoms at rest and severe symptoms with any activity. Hence the severity increased from class I (better) to Class IV (worse).
Time Frame
Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Title
Mean Oxygen Saturation in Blood Over Time
Description
Pulse oximetry (oxygen saturation) was analyzed. Data for Pulse oximetry (oxygen saturation) was analyzed up to the treatment follow up (1 week after Visit 3 [Week 4]).
Time Frame
up to the treatment follow up (1 week after Visit 3 [Week 4])
Title
Number of Participants With Urine Pregnancy Test Positive
Description
Urine samples were collected for urine pregnancy test. Urine samples were collected at up to the treatment follow up (1 week after Visit 3 [Week 4]). Number of participants with urine pregnancy test positive has been reported.
Time Frame
up to the treatment follow up (1 week after Visit 3 [Week 4])
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118-2393
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8550
Country
United States
Facility Name
GSK Investigational Site
City
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
25793960
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.
Results Reference
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Study of a New Thermo Stable Formulation of Epoprostenol Sodium to Treat Pulmonary Arterial Hypertension (PAH)
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