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This study is a Phase IV, open-label, single-arm study to assess the safety and the necessity of dose adjustment after switching to FLOLAN injection prepared with the reformulated diluent in Japanese patients with PAH who are receiving higher doses of FLOLAN injection than in other countries. The objective is to evaluate the safety and tolerability of the thermostable formulation of FLOLAN injection (that is [i.e.], FLOLAN injection prepared with the reformulated diluent) when switched from the existing FLOLAN injection treatment (i.e., FLOLAN injection prepared with the currently marketed diluent). The study will include a screening visit, a run-in period of a maximum of 4 weeks with the existing FLOLAN treatment (i.e., FLOLAN injection prepared with the currently marketed diluent), a 4-week treatment period with the thermostable formulation of FLOLAN injection (i.e., FLOLAN injection prepared with the reformulated diluent) and a one-week follow-up visit. Adequate number of subjects will be enrolled in the study in order to have 10 subjects to complete assessments at 4 weeks, including at least 5 subjects as a subset of subjects who consent to undergo right heart catheterisation (RHC) over 24-hour and at Week 4. FLOLAN is a registered trademark of the GlaxoSmithKline [GSK] group of companies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FLOLAN arm | Experimental | Subjects will receive the existing FLOLAN treatment (i.e., FLOLAN injection prepared with the currently marketed diluent) for a run-in period of a maximum of 4 weeks, the thermostable formulation of FLOLAN injection (i.e., FLOLAN injection prepared with the reformulated diluent) for a 4-week treatment period and there will be a one-week follow-up visit. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FLOLAN injection with currently marketed diluent | Drug | FLOLAN injection (epoprostenol 0.5 or 1.5) prepared with the currently marketed diluent (epoprostenol sodium+ powder of hydrogen [pH] 10.2 - 10.8 diluent) for Injection. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical interventions. Intention-to-Treat (ITT) population: comprised of all participants who have received at least one dose of the thermostable formulation of FLOLAN. | Up to Week 4 |
| Number of Participants With Mild, Moderate or Severe AEs | Intensity for an AE and SAE is categorized as mild if an event is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate if an event is sufficiently discomforting to interfere with normal everyday activities; severe if that prevents normal everyday activities. | Up to Week 4 |
| Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4 | Blood samples were collected for the measurement of percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in blood at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hour (hr) prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Hemoglobin at Baseline and Week 4 | Blood samples were collected for measurement of hemoglobin values at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Events to Adjust Dose of FLOLAN Based on the Change From Baseline to 3 Hours in Mean Pulmonary Artery Pressure (mPAP) | To assess the frequency of dose adjustment requirements based on the changes from baseline in mPAP up to 3 hours after dosing.The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Participants who gave consent to undergo right heart catheterisation (RHC) over 24-hour and at week 4 were assessed. Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. |
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Inclusion Criteria:
Male or female subjects at least 18 to 75 years at the time of screening;
Subjects must be on FLOLAN therapy for pulmonary arterial hypertension (PAH) as approved in the product label;
Subjects must receive FLOLAN therapy at 45 nanograms (ng)/kilogram (kg)/minute (min) or higher;
Subjects must be on stable doses of their existing FLOLAN treatment for a minimum of one month prior to screening; it is acceptable to adjust within 10% of dose during the last one month period;
Subjects must be on stable doses of any current PAH treatments other than FLOLAN therapy in the last 30 days prior to screening;
Subjects who meet any of the following: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative [serum or urine] human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:
Subject must agree not to participate in a clinical study involving another investigational drug or device throughout this study;
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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Okayama | 701-1192 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29608587 | Derived | Mihara K, Ogawa A, Matsubara H, Terao T, Ichikawa Y. Investigation of safety and efficacy of the new more thermostable formulation of Flolan (epoprostenol) in Japanese patients with pulmonary arterial hypertension (PAH)-An open-label, single-arm study. PLoS One. 2018 Apr 2;13(4):e0195195. doi: 10.1371/journal.pone.0195195. eCollection 2018. |
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Ten participants (par.) who gave consent and passed the screening assessments were enrolled in the Run-in period. After the Run-in period, par. underwent Baseline assessments and were switched to thermostable formulation of FLOLAN. All par. underwent right heart catheterisation (RHC) up to 24 hours and at Week 4 after switching to study treatment.
This study consisted a screening visit, a Run-in period of a maximum of 30 days observation, a 4-week treatment period with the thermostable formulation of FLOLAN, and a one-week follow-up visit.
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| ID | Title | Description |
|---|---|---|
| FG000 | FLOLAN With New Diluent | Japanese par. with pulmonary arterial hypertension (PAH) received FLOLAN prepared with the current marketed diluent (epoprostenol sodium + Potential of Hydrogen [pH] 10.2-10.8 diluent) for Injection in run-in period for a maximum of 30 days, and then switched to FLOLAN prepared with new diluent (epoprostenol sodium + pH 11.7-12.3 diluent) for Injection for 4-weeks in the treatment period. Par. received dose of 47.6 to 113.8 nanogram per kilogram per minute (ng/kg/min) during the treatment period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | FLOLAN With New Diluent | Japanese par. with pulmonary arterial hypertension (PAH) received FLOLAN prepared with the current marketed diluent (epoprostenol sodium + Potential of Hydrogen [pH] 10.2-10.8 diluent) for Injection in run-in period for a maximum of 30 days, and then switched to FLOLAN prepared with new diluent (epoprostenol sodium + pH 11.7-12.3 diluent) for Injection for 4-weeks in the treatment period. Par. received dose of 47.6 to 113.8 nanogram per kilogram per minute (ng/kg/min) during the treatment period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical interventions. Intention-to-Treat (ITT) population: comprised of all participants who have received at least one dose of the thermostable formulation of FLOLAN. | ITT population | Posted | Number | Participants | Up to Week 4 |
|
AEs and SAEs will be collected from the start of treatment with the thermostable formulation of FLOLAN until the follow-up contact (approximately up to Day 65).
SAEs and non-serious AEs were collected in Intention-to-Treat (ITT) population, comprising of all participants who have received at least one dose of the thermostable formulation of FLOLAN.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FLOLAN With New Diluent | Japanese par. with pulmonary arterial hypertension (PAH) received FLOLAN prepared with the current marketed diluent (epoprostenol sodium + Potential of Hydrogen [pH] 10.2-10.8 diluent) for Injection in run-in period for a maximum of 30 days, and then switched to FLOLAN prepared with new diluent (epoprostenol sodium + pH 11.7-12.3 diluent) for Injection for 4-weeks in the treatment period. Par. received dose of 47.6 to 113.8 nanogram per kilogram per minute (ng/kg/min) during the treatment period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D011464 | Epoprostenol |
| ID | Term |
|---|---|
| D044062 | Prostaglandins I |
| D011453 | Prostaglandins |
| D015777 | Eicosanoids |
| D005231 | Fatty Acids, Unsaturated |
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| FLOLAN injection with reformulated diluent | Drug | FLOLAN injection (epoprostenol 0.5 or 1.5) prepared with the reformulated diluent (epoprostenol sodium + pH 11.7 - 12.3 diluent) for Injection. |
|
| Absolute Values of Hematocrit at Baseline and Week 4 | Blood samples were collected for measurement of hematocrit values at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4 | Blood samples were collected for measurement of platelets and white blood cells (WBC) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Red Blood Cell Count at Baseline and Week 4 | Blood samples were collected for measurement of red blood cells at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Albumin and Total Protein at Baseline and Week 4 | Blood samples were collected for measurement of albumin and total protein at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4 | Blood samples were collected for measurement of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4 | Blood samples were collected for measurement of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Gamma Glutamyltransferase (GGT), Lactate Dehydrogenase (LDH) and Creatine Kinase (CK) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4 | Blood samples were collected for measurement of urea/Blood Urea Nitrogen (Urea/BUN), glucose, chloride, sodium, potassium, magnesium, phosphorus, inorganic, and calcium at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4 | Blood samples were collected for measurement of Free Triiodothyronine (FT3) and Free Thyroxine (FT4) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Absolute Values of Thyroid Stimulating Hormone at Baseline and Week 4 | Blood samples were collected for measurement of Thyroid Stimulating Hormone (TSH) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline and Week 4 |
| Number of Participants With the Indicated Urinalysis Findings | Urine protein, urine glucose, and occult blood were assessed at Baseline (BL) and Week 4 (W4). Dipstick test was performed for routine urinalysis. Abnormal values such as trace, 1+, 2+, 3+ and positive have been reported. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). | Baseline and Week 4 |
| Number of Participants With the Indicated Electrocardiogram (ECG) Findings | A safety 12-lead ECG was performed at Baseline (BL), 24 hr after switching to the new Flolan diluent and Week 4 (W4). Any abnormal clinically significant (CS) and not clinically significant (NCS) findings were reported. ECG abnormaility with respect to CS and NCS findings were judged by the investigator. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Baseline, 24 hour and Week 4 |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured at Baseline, 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline, 1 hour, 3 hour, 24 hour and Week 4 |
| Change From Baseline in Heart Rate | Heart rate was measured at Baseline, 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline and up to Week 4 |
| Change From Baseline in Body Weight | Body weight was measured at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. Participants with body weight outside and within the clinical concern reference range (<50kg) has been presented. | Baseline and Week 4 |
| Absolute Values of Oxygen Saturation | Oxygen saturation was measured by pulse oximetry at Baseline (BL), 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). | Baseline and up to Week 4 |
| Up to Week 4 |
| Number of Participants With the Reason for the Change Dose of the Thermostable Formulation of FLOLAN | All reasons for FLOLAN dose adjustments after the switch were listed. | Up to Week 4 |
| Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT Pro BNP) | Blood samples were collected at Baseline, 24 hours after the first dose of thermostable formulation of FLOLAN, and Week 4 for measurement of NT pro BNP. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline and up to Week 4 |
| Number of Participants in Each World Health Organization (WHO) Functional Class | The WHO functional classes of PAH range from Class I (without limitation in physical activity) to Class IV (inability to perform a physical activity without any symptoms). | Baseline and Week 4 |
| Number of Participants With Change of WHO Functional Class From Previous Visit | WHO Functional Classification of physical activity limitations: I (no limitation) and IV (unable to carry out any physical activity without symptoms). The change from baseline in WHO class was classified as Improved (decrease in functional class), No Change (functional class stayed the same), and Deteriorated (functional class increased). The change from baseline in WHO functional class at Week 4 has been presented in the table. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | Up to Week 4 |
| Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) | mPAP and mRAP are hemodynamic parameters. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline and up to Week 4 |
| Change From Baseline in Pulmonary Vascular Resist (PVR) | The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline and up to Week 4 |
| Change From Baseline in Cardiac Output (CO) | Cardiac output is the volume of blood pumped by the heart per minute. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | Baseline and up to Week 4 |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
|
Japanese par. with pulmonary arterial hypertension (PAH) received FLOLAN prepared with the current marketed diluent (epoprostenol sodium + Potential of Hydrogen [pH] 10.2-10.8 diluent) for Injection in run-in period for a maximum of 30 days, and then switched to FLOLAN prepared with new diluent (epoprostenol sodium + pH 11.7-12.3 diluent) for Injection for 4-weeks in the treatment period. Par. received dose of 47.6 to 113.8 nanogram per kilogram per minute (ng/kg/min) during the treatment period.
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| Primary | Number of Participants With Mild, Moderate or Severe AEs | Intensity for an AE and SAE is categorized as mild if an event is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate if an event is sufficiently discomforting to interfere with normal everyday activities; severe if that prevents normal everyday activities. | ITT population | Posted | Number | Participants | Up to Week 4 |
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| Primary | Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4 | Blood samples were collected for the measurement of percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in blood at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hour (hr) prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Percentage | Baseline and Week 4 |
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| Primary | Absolute Values of Hemoglobin at Baseline and Week 4 | Blood samples were collected for measurement of hemoglobin values at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Gram/Liter (G/L) | Baseline and Week 4 |
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| Primary | Absolute Values of Hematocrit at Baseline and Week 4 | Blood samples were collected for measurement of hematocrit values at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Liter (L) | Baseline and Week 4 |
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| Primary | Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4 | Blood samples were collected for measurement of platelets and white blood cells (WBC) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Giga/Liter (GI/L) | Baseline and Week 4 |
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| Primary | Absolute Values of Red Blood Cell Count at Baseline and Week 4 | Blood samples were collected for measurement of red blood cells at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | terabinary/liter (Ti/L)) | Baseline and Week 4 |
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| Primary | Absolute Values of Albumin and Total Protein at Baseline and Week 4 | Blood samples were collected for measurement of albumin and total protein at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | G/L | Baseline and Week 4 |
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| Primary | Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4 | Blood samples were collected for measurement of total and direct bilirubin, creatinine (CRT), and uric acid (UA) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline and Week 4 |
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| Primary | Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4 | Blood samples were collected for measurement of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Gamma Glutamyltransferase (GGT), Lactate Dehydrogenase (LDH) and Creatine Kinase (CK) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | International units per liter (IU/L) | Baseline and Week 4 |
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| Primary | Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4 | Blood samples were collected for measurement of urea/Blood Urea Nitrogen (Urea/BUN), glucose, chloride, sodium, potassium, magnesium, phosphorus, inorganic, and calcium at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | Millimoles per litre (mmol/L) | Baseline and Week 4 |
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| Primary | Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4 | Blood samples were collected for measurement of Free Triiodothyronine (FT3) and Free Thyroxine (FT4) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | picomoles per litre (pmol/L) | Baseline and Week 4 |
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| Primary | Absolute Values of Thyroid Stimulating Hormone at Baseline and Week 4 | Blood samples were collected for measurement of Thyroid Stimulating Hormone (TSH) at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Mean | Standard Deviation | milliunits per litre (mU/L) | Baseline and Week 4 |
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| Primary | Number of Participants With the Indicated Urinalysis Findings | Urine protein, urine glucose, and occult blood were assessed at Baseline (BL) and Week 4 (W4). Dipstick test was performed for routine urinalysis. Abnormal values such as trace, 1+, 2+, 3+ and positive have been reported. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). | ITT population | Posted | Number | Participants | Baseline and Week 4 |
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| Primary | Number of Participants With the Indicated Electrocardiogram (ECG) Findings | A safety 12-lead ECG was performed at Baseline (BL), 24 hr after switching to the new Flolan diluent and Week 4 (W4). Any abnormal clinically significant (CS) and not clinically significant (NCS) findings were reported. ECG abnormaility with respect to CS and NCS findings were judged by the investigator. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Number | Participants | Baseline, 24 hour and Week 4 |
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| Primary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured at Baseline, 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline, 1 hour, 3 hour, 24 hour and Week 4 |
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| Primary | Change From Baseline in Heart Rate | Heart rate was measured at Baseline, 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Mean | Standard Deviation | Beats per minute (bpm) | Baseline and up to Week 4 |
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| Primary | Change From Baseline in Body Weight | Body weight was measured at Baseline (BL) and Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. Participants with body weight outside and within the clinical concern reference range (<50kg) has been presented. | ITT population | Posted | Number | Participants | Baseline and Week 4 |
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| Primary | Absolute Values of Oxygen Saturation | Oxygen saturation was measured by pulse oximetry at Baseline (BL), 1 hr, 3 hr, 24 hr, Week 4 (W4). The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). | ITT population | Posted | Mean | Standard Deviation | Percentage | Baseline and up to Week 4 |
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| Secondary | Number of Events to Adjust Dose of FLOLAN Based on the Change From Baseline to 3 Hours in Mean Pulmonary Artery Pressure (mPAP) | To assess the frequency of dose adjustment requirements based on the changes from baseline in mPAP up to 3 hours after dosing.The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Participants who gave consent to undergo right heart catheterisation (RHC) over 24-hour and at week 4 were assessed. Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Number | Number of events | Up to Week 4 |
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| Secondary | Number of Participants With the Reason for the Change Dose of the Thermostable Formulation of FLOLAN | All reasons for FLOLAN dose adjustments after the switch were listed. | ITT Population | Posted | Number | Participants | Up to Week 4 |
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| Secondary | Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT Pro BNP) | Blood samples were collected at Baseline, 24 hours after the first dose of thermostable formulation of FLOLAN, and Week 4 for measurement of NT pro BNP. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Mean | Standard Deviation | nanogram/liter | Baseline and up to Week 4 |
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|
|
| Secondary | Number of Participants in Each World Health Organization (WHO) Functional Class | The WHO functional classes of PAH range from Class I (without limitation in physical activity) to Class IV (inability to perform a physical activity without any symptoms). | ITT population | Posted | Number | Participants | Baseline and Week 4 |
|
|
|
| Secondary | Number of Participants With Change of WHO Functional Class From Previous Visit | WHO Functional Classification of physical activity limitations: I (no limitation) and IV (unable to carry out any physical activity without symptoms). The change from baseline in WHO class was classified as Improved (decrease in functional class), No Change (functional class stayed the same), and Deteriorated (functional class increased). The change from baseline in WHO functional class at Week 4 has been presented in the table. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline') | ITT population | Posted | Number | Participants | Up to Week 4 |
|
|
|
| Secondary | Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) | mPAP and mRAP are hemodynamic parameters. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT Population | Posted | Mean | Standard Deviation | mmHg | Baseline and up to Week 4 |
|
|
|
| Secondary | Change From Baseline in Pulmonary Vascular Resist (PVR) | The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Mean | Standard Deviation | millimeter mercury/liter/minute | Baseline and up to Week 4 |
|
|
|
| Secondary | Change From Baseline in Cardiac Output (CO) | Cardiac output is the volume of blood pumped by the heart per minute. The Baseline values are those collected within 0.5 hr prior to the first dose of the new diluent formulation ('Visit 2 - Baseline'). Change from Baseline is defined as the difference between the post-dose visit value and the Baseline value. | ITT population | Posted | Mean | Standard Deviation | liter/minute | Baseline and up to Week 4 |
|
|
|
| 0 |
| 10 |
| 2 |
| 10 |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| Title | Measurements |
|---|---|
|
| Eosinophils W4 |
|
| Lymphocytes BL |
|
| Lymphocytes W4 |
|
| Monocytes BL |
|
| Monocytes W4 |
|
| Total Neutrophils BL |
|
| Total Neutrophils W4 |
|
| Title | Measurements |
|---|---|
|
| WBC count, W4 |
|
| Title | Measurements |
|---|---|
|
| Total protein, W4 |
|
| Title | Measurements |
|---|---|
|
| Direct Bilirubin, W4 |
|
| CRT, BL |
|
| CRT, W4 |
|
| UA, BL |
|
| UA, W4 |
|
| Title | Measurements |
|---|---|
|
| AST, W4 |
|
| ALP, BL |
|
| ALP, W4 |
|
| GGT, BL |
|
| GGT, W4 |
|
| LDH, BL |
|
| LDH, W4 |
|
| CK, BL |
|
| CK, W4 |
|
| Title | Measurements |
|---|---|
|
| Glucose, W4 |
|
| Chloride, BL |
|
| Chloride, W4 |
|
| Sodium, BL |
|
| Sodium, W4 |
|
| Potassium, BL |
|
| Potassium, W4 |
|
| Magnesium, BL |
|
| Magnesium, W4 |
|
| Phosphorus, inorganic, BL |
|
| Phosphorus, inorganic, W4 |
|
| Calcium, BL |
|
| Calcium, W4 |
|
| Title | Measurements |
|---|---|
|
| FT4, W4 |
|
| Title | Measurements |
|---|---|
|
| Urine glucose, BL, 3+ |
|
| Urine glucose, BL, Positive |
|
| Urine glucose, W4, Trace |
|
| Urine glucose, W4, 1+ |
|
| Urine glucose, W4, 2+ |
|
| Urine glucose, W4, 3+ |
|
| Urine glucose, W4, Positive |
|
| Urine occult blood, BL, Trace |
|
| Urine occult blood, BL, 1+ |
|
| Urine occult blood, BL, 2+ |
|
| Urine occult blood, BL, 3+ |
|
| Urine occult blood, BL, Positive |
|
| Urine occult blood, W4, Trace |
|
| Urine occult blood, W4, 1+ |
|
| Urine occult blood, W4, 2+ |
|
| Urine occult blood, W4, 3+ |
|
| Urine occult blood, W4, Positive |
|
| Urine protein, BL, Trace |
|
| Urine protein, BL, 1+ |
|
| Urine protein, BL, 2+ |
|
| Urine protein, BL, 3+ |
|
| Urine protein, BL, Positive |
|
| Urine protein, W4, Trace |
|
| Urine protein, W4, 1+ |
|
| Urine protein, W4, 2+ |
|
| Urine protein, W4, 3+ |
|
| Urine protein, W4, Positive |
|
| Title | Measurements |
|---|
|
| 24 hr, CS |
|
| W4, NCS |
|
| W4, CS |
|
| Title | Measurements |
|---|---|
|
| SBP, Week 4 |
|
| DBP, 1 hr |
|
| DBP, 3 hr |
|
| DBP, 24 hr |
|
| DBP, Week 4 |
|
| Title | Measurements |
|---|---|
|
| Week 4 |
|
| Title | Measurements |
|---|---|
|
| < clinical concern range, W4 |
|
| Title | Measurements |
|---|---|
|
| 24 hr |
|
| Week 4 |
|
| Title | Measurements |
|---|---|
|
| WHO Class IV, BL |
|
| WHO Class I, W4 |
|
| WHO Class II, W4 |
|
| WHO Class III, W4 |
|
| WHO Class IV, W4 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| mPAP, Week4 |
|
| mRAP, 1hr |
|
| mRAP, 3hr |
|
| mRAP, 24hr |
|
| mRAP, Week4 |
|
| Title | Measurements |
|---|---|
|
| Week 4 |
|
| Title | Measurements |
|---|---|
|
| Week 4 |
|