Hypertension, Pulmonary
Conditions
Keywords
flolan, pulmonary arterial hypertension, thermo stable formulation, epoprostenol sodium, modified sterile diluent
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.
Interventions
DRUGcurrent marketed FLOLAN (epoprostenol sodium)
continuous intravenous infusion
DRUGnew thermo stable formulation of epoprostenol sodium
continuous intravenous infusion
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3) | 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 | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3). | 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 | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Vital Signs at Week 4: Heart Rate | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4 | 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 | Up to 1 week after Week 4 (Follow-up) | 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 | Up to 1 week after Week 4 (Follow-up) | 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 | Up to 1 week after Week 4 (Follow-up) | Dipstick method was used to measure blood, glucose and protein. Data was analyzed up to 1 week after Week 4 (Follow-up visit). |
| Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs) | Up to visit 3 (Week 4) | 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. |
| Breathlessness After 6MWD - Borg Dyspnoea Index (BDI) | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4 | 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 | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 | 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 | up to the treatment follow up (1 week after Visit 3 [Week 4]) | 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 | up to the treatment follow up (1 week after Visit 3 [Week 4]) | 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. |
| Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 | 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). |
| Number of Participants With Infusion Site Reactions During Treatment Period | Baseline visit (Visit 2) to Week 4 (Visit 3) | 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 | Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4(Visit 3) | 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). |
Countries
Canada, Netherlands, United States
Participant flow
Recruitment details
A total of 17 participants were recruited from 23 November 2011 to 16 May 2012, out of which 16 participants entered the treatment phase. Study was conducted across 5 centres in the United States, 1 centre in Canada and 1 centre in the Netherlands.
Pre-assignment details
There was a 4-week run-in period during which 1 participant was assessed to be a screen failure at the Baseline Visit (Visit 2) due to the participant self-titrating their epoprostenol sodium. During the 4-week run-in period, participants received currently marketed epoprostenol sodium.
Participants by arm
| Arm | Count |
|---|---|
| Epoprostenol Sodium for Injection Participants received new thermo stable 100 mL formulation of epoprostenol sodium via intravenous infusion each day for 4-week treatment period. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Epoprostenol Sodium for Injection |
|---|---|
| Age, Continuous | 50.0 Years STANDARD_DEVIATION 13.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 9 / 16 |
| serious Total, serious adverse events | 2 / 16 |
Outcome results
Primary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Dose of Thermo Stable Epoprostenol Sodium at Week 4 | 0.22 ng/kg/min | Standard Deviation 1.169 |
Primary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3)
Population: Intent-to-Treat (ITT) population consisted of all participants who received at least one dose of epoprostenol sodium during the Run-in period (either currently marketed epoprostenol sodium or the study drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Physical Functioning | -1.156 Score on a scale | Standard Deviation 3.6593 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Role-Physical | -0.765 Score on a scale | Standard Deviation 6.305 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Role-Emotional | 0.002 Score on a scale | Standard Deviation 11.1773 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Vitality | 0.781 Score on a scale | Standard Deviation 7.1636 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Mental Health | 0.883 Score on a scale | Standard Deviation 7.6063 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Social Functioning | 1.706 Score on a scale | Standard Deviation 7.1043 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Bodily Pain | 3.065 Score on a scale | Standard Deviation 5.8291 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | General Health | -0.606 Score on a scale | Standard Deviation 5.6068 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Physical Health Component | -0.123 Score on a scale | Standard Deviation 4.2876 |
| Epoprostenol Sodium for Injection | Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) | Mental Health Component | 1.141 Score on a scale | Standard Deviation 6.5078 |
Primary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4 (Visit 3).
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q2- ability to perform physical activities | -0.9 Score on a scale | Standard Deviation 2.29 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q3- ability to perform your basic daily activies | -1.5 Score on a scale | Standard Deviation 1.86 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q4- ability to perform activities with your family | -0.8 Score on a scale | Standard Deviation 2.37 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q5- ability to participate in social activities | -0.9 Score on a scale | Standard Deviation 1.88 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q6- ability to comply with your Flolan treatment | 0.3 Score on a scale | Standard Deviation 3.34 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q7- ability to perform new activity(Jogging, walk) | 0.4 Score on a scale | Standard Deviation 2 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q8- overall satisfaction | 0.4 Score on a scale | Standard Deviation 1.09 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q9- interested physical activity | -0.1 Score on a scale | Standard Deviation 2.53 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q10- feel physically restricted from participating | 0.1 Score on a scale | Standard Deviation 2.73 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q11- confident in my ability to do new activity | 0.6 Score on a scale | Standard Deviation 2.5 |
| Epoprostenol Sodium for Injection | Change From Baseline in Study Specific Participant Acceptance Survey | Q12- treatment regimen constantly weighs on mind | -0.6 Score on a scale | Standard Deviation 1.75 |
Secondary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Breathlessness After 6MWD - Borg Dyspnoea Index (BDI) | 0.36 Score on a scale | Standard Deviation 0.535 |
Secondary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Six Minute Walk Distance Test (6MWD) After 4-weeks of Treatment | -3.55 meters | Standard Deviation 45.321 |
Secondary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) to Week 4
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Vital Signs at Week 4: Heart Rate | -1.7 beats/min | Standard Deviation 8.52 |
Secondary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4(Visit 3)
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoprostenol Sodium for Injection | Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure | Systolic blood pressure | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 11.47 |
| Epoprostenol Sodium for Injection | Change From Baseline in Vital Signs at Week 4 : Systolic and Diastolic Blood Pressure | Diastolic blood pressure | 0.4 Millimeter of mercury (mmHg) | Standard Deviation 10.99 |
Secondary
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 \[Week 4\]).
Time frame: up to the treatment follow up (1 week after Visit 3 [Week 4])
Population: ITT population. Only those participant available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoprostenol Sodium for Injection | Mean Oxygen Saturation in Blood Over Time | Week 4 | 94.5 Percentage of oxygen in blood | Standard Deviation 2.58 |
| Epoprostenol Sodium for Injection | Mean Oxygen Saturation in Blood Over Time | Follow-up (1 week after Week 4) | 93.0 Percentage of oxygen in blood | — |
| Epoprostenol Sodium for Injection | Mean Oxygen Saturation in Blood Over Time | Baseline | 94.3 Percentage of oxygen in blood | Standard Deviation 1.95 |
Secondary
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.
Time frame: Up to 1 week after Week 4 (Follow-up)
Population: ITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Clinical Chemistry | 0 Participants |
Secondary
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).
Time frame: Up to 1 week after Week 4 (Follow-up)
Population: ITT population. Only those participant available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Hemoglobin (G/L) : Week 4: high | 1 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Hematocrit (1): Screening: Low | 14 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Hematocrit (1): Baseline: Low | 15 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Hematocrit (1): Week 4: Low | 15 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Hematocrit (1): Follow-up: Low | 1 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Platelet count (GI/L): Screening: Low | 5 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Platelet count (GI/L): Baseline: Low | 2 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Platelet count (GI/L): Week 4: Low | 1 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Hematology | Platelet count (GI/L): Follow up: Low | 1 Participants |
Secondary
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).
Time frame: Up to 1 week after Week 4 (Follow-up)
Population: ITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Abnormal Urinalysis | 0 Participants |
Secondary
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.
Time frame: Up to visit 3 (Week 4)
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs) | Any AEs | 9 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Any Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events(SAEs) | Any SAEs | 1 Participants |
Secondary
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.
Time frame: Baseline visit (Visit 2) to Week 4 (Visit 3)
Population: ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Infusion Site Reactions During Treatment Period | Erythema | 1 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Infusion Site Reactions During Treatment Period | Signs of local sepsis | 1 Participants |
| Epoprostenol Sodium for Injection | Number of Participants With Infusion Site Reactions During Treatment Period | Other | 1 Participants |
Secondary
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.
Time frame: up to the treatment follow up (1 week after Visit 3 [Week 4])
Population: ITT population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoprostenol Sodium for Injection | Number of Participants With Urine Pregnancy Test Positive | 0 Participants |
Secondary
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).
Time frame: Baseline (Visit 2 i.e. Day-14 [+ or - 7 days]) and Week 4
Population: ITT population. Only those participants with data available at the specified time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Baseline WHO Class I | 2 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Baseline WHO Class II | 9 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Baseline WHO Class III | 4 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Baseline WHO Class IV | 0 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Week 4 Class I | 2 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Week 4 Class II | 10 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Week 4 Class III | 4 Participants |
| Epoprostenol Sodium for Injection | World Health Organization [WHO] Functional Class at Baseline and After 4- Weeks of Treatment | Week 4 Class IV | 0 Participants |