Trial Outcomes & Findings for Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects (NCT NCT02705807)
NCT ID: NCT02705807
Last Updated: 2017-04-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
10 participants
Primary outcome timeframe
Up to Week 4
Results posted on
2017-04-06
Participant Flow
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.
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.
Participant milestones
| Measure |
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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|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of a New Thermostable Formulation of FLOLAN in Japanese Subjects
Baseline characteristics by cohort
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
|
Age, Continuous
|
35.8 Years
STANDARD_DEVIATION 7.35 • n=93 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Asian - Japanese Heritage
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10 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
|
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Any AE
|
2 Participants
|
|
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Any Drug-Related AE
|
1 Participants
|
|
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Any SAE
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
|
Number of Participants With Mild, Moderate or Severe AEs
Mild, Nausea
|
1 Participants
|
|
Number of Participants With Mild, Moderate or Severe AEs
Mild, Hepatic function abnormal
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Basophils BL
|
0.61 Percentage
Standard Deviation 0.331
|
|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Basophils W4
|
0.45 Percentage
Standard Deviation 0.321
|
|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Eosinophils BL
|
2.66 Percentage
Standard Deviation 1.789
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|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Eosinophils W4
|
3.25 Percentage
Standard Deviation 3.221
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|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Lymphocytes BL
|
22.87 Percentage
Standard Deviation 4.181
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Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Lymphocytes W4
|
22.37 Percentage
Standard Deviation 6.453
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|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Monocytes BL
|
5.16 Percentage
Standard Deviation 1.766
|
|
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Monocytes W4
|
4.46 Percentage
Standard Deviation 1.710
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Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Total Neutrophils BL
|
68.70 Percentage
Standard Deviation 6.134
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Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in Blood at Baseline and Week 4
Total Neutrophils W4
|
69.47 Percentage
Standard Deviation 8.623
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PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Absolute Values of Hemoglobin at Baseline and Week 4
BL
|
135.5 Gram/Liter (G/L)
Standard Deviation 13.37
|
|
Absolute Values of Hemoglobin at Baseline and Week 4
W4
|
124.1 Gram/Liter (G/L)
Standard Deviation 10.31
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Absolute Values of Hematocrit at Baseline and Week 4
BL
|
0.3969 Liter (L)
Standard Deviation 0.03230
|
|
Absolute Values of Hematocrit at Baseline and Week 4
W4
|
0.3662 Liter (L)
Standard Deviation 0.02682
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4
Platelet count, BL
|
181.9 Giga/Liter (GI/L)
Standard Deviation 75.46
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Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4
Platelet count, W4
|
153.4 Giga/Liter (GI/L)
Standard Deviation 51.58
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Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4
WBC count, BL
|
0.0065 Giga/Liter (GI/L)
Standard Deviation 0.00125
|
|
Absolute Values of Platelet Count and White Blood Cell Count at Baseline and Week 4
WBC count, W4
|
0.0063 Giga/Liter (GI/L)
Standard Deviation 0.00140
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PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
|
Absolute Values of Red Blood Cell Count at Baseline and Week 4
BL
|
0.0482 terabinary/liter (Ti/L))
Standard Deviation 0.00357
|
|
Absolute Values of Red Blood Cell Count at Baseline and Week 4
W4
|
0.0446 terabinary/liter (Ti/L))
Standard Deviation 0.00344
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Absolute Values of Albumin and Total Protein at Baseline and Week 4
Albumin, BL
|
43.8 G/L
Standard Deviation 6.03
|
|
Absolute Values of Albumin and Total Protein at Baseline and Week 4
Albumin, W4
|
41.1 G/L
Standard Deviation 2.64
|
|
Absolute Values of Albumin and Total Protein at Baseline and Week 4
Total protein, BL
|
68.0 G/L
Standard Deviation 7.27
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|
Absolute Values of Albumin and Total Protein at Baseline and Week 4
Total protein, W4
|
63.9 G/L
Standard Deviation 4.51
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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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|---|---|
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Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
Total Bilirubin, BL
|
9.063 Micromoles per liter
Standard Deviation 2.9120
|
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Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
Total Bilirubin, W4
|
8.550 Micromoles per liter
Standard Deviation 3.2244
|
|
Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
Direct Bilirubin, BL
|
0.855 Micromoles per liter
Standard Deviation 0.9012
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Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
Direct Bilirubin, W4
|
1.368 Micromoles per liter
Standard Deviation 1.0815
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|
Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
CRT, BL
|
58.1672 Micromoles per liter
Standard Deviation 7.19132
|
|
Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
CRT, W4
|
50.4764 Micromoles per liter
Standard Deviation 8.28689
|
|
Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
UA, BL
|
349.1476 Micromoles per liter
Standard Deviation 93.83901
|
|
Absolute Values of Total and Direct Bilirubin, Creatinine, and Uric Acid at Baseline and Week 4
UA, W4
|
313.4596 Micromoles per liter
Standard Deviation 70.10066
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
ALT, BL
|
15.9 International units per liter (IU/L)
Standard Deviation 7.56
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
ALT, W4
|
19.6 International units per liter (IU/L)
Standard Deviation 21.71
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
AST, BL
|
14.0 International units per liter (IU/L)
Standard Deviation 3.89
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
AST, W4
|
16.4 International units per liter (IU/L)
Standard Deviation 11.35
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
ALP, BL
|
181.0 International units per liter (IU/L)
Standard Deviation 57.02
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
ALP, W4
|
175.2 International units per liter (IU/L)
Standard Deviation 69.45
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
GGT, BL
|
22.7 International units per liter (IU/L)
Standard Deviation 17.46
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
GGT, W4
|
22.1 International units per liter (IU/L)
Standard Deviation 17.69
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
LDH, BL
|
165.2 International units per liter (IU/L)
Standard Deviation 33.77
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
LDH, W4
|
160.8 International units per liter (IU/L)
Standard Deviation 34.81
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
CK, BL
|
40.8 International units per liter (IU/L)
Standard Deviation 15.13
|
|
Absolute Values of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Gamma Glutamyltransferase, Lactate Dehydrogenase and Creatine Kinase at Baseline and Week 4
CK, W4
|
44.7 International units per liter (IU/L)
Standard Deviation 17.22
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Urea/BUN, BL
|
4.6767 Millimoles per litre (mmol/L)
Standard Deviation 1.07034
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Urea/BUN, W4
|
4.4625 Millimoles per litre (mmol/L)
Standard Deviation 0.99917
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Glucose, BL
|
4.9959 Millimoles per litre (mmol/L)
Standard Deviation 0.34814
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Glucose, W4
|
5.7675 Millimoles per litre (mmol/L)
Standard Deviation 2.05053
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Chloride, BL
|
103.8 Millimoles per litre (mmol/L)
Standard Deviation 4.64
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Chloride, W4
|
103.9 Millimoles per litre (mmol/L)
Standard Deviation 4.01
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Sodium, BL
|
139.6 Millimoles per litre (mmol/L)
Standard Deviation 1.96
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Sodium, W4
|
138.0 Millimoles per litre (mmol/L)
Standard Deviation 1.76
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Potassium, BL
|
3.61 Millimoles per litre (mmol/L)
Standard Deviation 0.373
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Potassium, W4
|
3.56 Millimoles per litre (mmol/L)
Standard Deviation 0.255
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Magnesium, BL
|
0.8467 Millimoles per litre (mmol/L)
Standard Deviation 0.06767
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Magnesium, W4
|
0.7891 Millimoles per litre (mmol/L)
Standard Deviation 0.03242
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Phosphorus, inorganic, BL
|
1.2399 Millimoles per litre (mmol/L)
Standard Deviation 0.15686
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Phosphorus, inorganic, W4
|
1.1947 Millimoles per litre (mmol/L)
Standard Deviation 0.19553
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Calcium, BL
|
2.2380 Millimoles per litre (mmol/L)
Standard Deviation 0.13100
|
|
Absolute Values of Urea/Blood Urea Nitrogen, Glucose, Chloride, Sodium, Potassium, Magnesium, Phosphorus (Inorganic), and Calcium at Baseline and Week 4
Calcium, W4
|
2.1357 Millimoles per litre (mmol/L)
Standard Deviation 0.07174
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4
FT3, BL
|
5.0974 picomoles per litre (pmol/L)
Standard Deviation 1.26044
|
|
Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4
FT3, W4
|
4.9280 picomoles per litre (pmol/L)
Standard Deviation 0.47048
|
|
Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4
FT4, BL
|
14.6847 picomoles per litre (pmol/L)
Standard Deviation 3.46426
|
|
Absolute Values of Free Triiodothyronine and Free Thyroxine at Baseline and Week 4
FT4, W4
|
14.2857 picomoles per litre (pmol/L)
Standard Deviation 2.47336
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Absolute Values of Thyroid Stimulating Hormone at Baseline and Week 4
TSH, BL
|
2.426 milliunits per litre (mU/L)
Standard Deviation 4.4045
|
|
Absolute Values of Thyroid Stimulating Hormone at Baseline and Week 4
TSH, W4
|
1.822 milliunits per litre (mU/L)
Standard Deviation 2.5287
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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').
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, BL, Trace
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, BL, 1+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, BL, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, BL, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, BL, Positive
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, W4, Trace
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, W4, 1+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, W4, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, W4, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine glucose, W4, Positive
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, BL, Trace
|
2 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, BL, 1+
|
1 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, BL, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, BL, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, BL, Positive
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, W4, Trace
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, W4, 1+
|
1 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, W4, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, W4, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine occult blood, W4, Positive
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, BL, Trace
|
5 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, BL, 1+
|
1 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, BL, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, BL, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, BL, Positive
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, W4, Trace
|
2 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, W4, 1+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, W4, 2+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, W4, 3+
|
0 Participants
|
|
Number of Participants With the Indicated Urinalysis Findings
Urine protein, W4, Positive
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, 24 hour and Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
BL, NCS
|
9 Participants
|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
BL, CS
|
1 Participants
|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
24 hr, NCS
|
9 Participants
|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
24 hr, CS
|
1 Participants
|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
W4, NCS
|
10 Participants
|
|
Number of Participants With the Indicated Electrocardiogram (ECG) Findings
W4, CS
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 hour, 3 hour, 24 hour and Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 1 hr
|
4.2 Millimeters of mercury (mmHg)
Standard Deviation 5.77
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 3 hr
|
1.2 Millimeters of mercury (mmHg)
Standard Deviation 7.73
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 24 hr
|
1.1 Millimeters of mercury (mmHg)
Standard Deviation 10.17
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 4
|
2.1 Millimeters of mercury (mmHg)
Standard Deviation 8.12
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 1 hr
|
-0.6 Millimeters of mercury (mmHg)
Standard Deviation 8.06
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 3 hr
|
0.7 Millimeters of mercury (mmHg)
Standard Deviation 5.52
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 24 hr
|
0.9 Millimeters of mercury (mmHg)
Standard Deviation 6.98
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 4
|
2.5 Millimeters of mercury (mmHg)
Standard Deviation 8.03
|
PRIMARY outcome
Timeframe: Baseline and up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Heart Rate
1 hr
|
1.4 Beats per minute (bpm)
Standard Deviation 11.57
|
|
Change From Baseline in Heart Rate
3 hr
|
2.3 Beats per minute (bpm)
Standard Deviation 11.54
|
|
Change From Baseline in Heart Rate
24 hr
|
5.1 Beats per minute (bpm)
Standard Deviation 9.27
|
|
Change From Baseline in Heart Rate
Week 4
|
4.0 Beats per minute (bpm)
Standard Deviation 9.76
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Body Weight
> clinical concern range, BL
|
0 Participants
|
|
Change From Baseline in Body Weight
< clinical concern range, BL
|
6 Participants
|
|
Change From Baseline in Body Weight
> clinical concern range, W4
|
0 Participants
|
|
Change From Baseline in Body Weight
< clinical concern range, W4
|
6 Participants
|
PRIMARY outcome
Timeframe: Baseline and up to Week 4Population: ITT population
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').
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Absolute Values of Oxygen Saturation
BL
|
97.6 Percentage
Standard Deviation 0.70
|
|
Absolute Values of Oxygen Saturation
1 hr
|
98.0 Percentage
Standard Deviation 1.15
|
|
Absolute Values of Oxygen Saturation
3 hr
|
97.6 Percentage
Standard Deviation 1.51
|
|
Absolute Values of Oxygen Saturation
24 hr
|
97.7 Percentage
Standard Deviation 1.16
|
|
Absolute Values of Oxygen Saturation
Week 4
|
97.8 Percentage
Standard Deviation 1.55
|
SECONDARY outcome
Timeframe: Up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Events to Adjust Dose of FLOLAN Based on the Change From Baseline to 3 Hours in Mean Pulmonary Artery Pressure (mPAP)
Yes
|
0 Number of events
|
|
Number of Events to Adjust Dose of FLOLAN Based on the Change From Baseline to 3 Hours in Mean Pulmonary Artery Pressure (mPAP)
No
|
10 Number of events
|
SECONDARY outcome
Timeframe: Up to Week 4Population: ITT Population
All reasons for FLOLAN dose adjustments after the switch were listed.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Participants With the Reason for the Change Dose of the Thermostable Formulation of FLOLAN
Adverse event
|
0 Participants
|
|
Number of Participants With the Reason for the Change Dose of the Thermostable Formulation of FLOLAN
Other
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline and up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT Pro BNP)
24 hr
|
-1.8 nanogram/liter
Standard Deviation 21.14
|
|
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT Pro BNP)
Week 4
|
33.7 nanogram/liter
Standard Deviation 103.66
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: ITT population
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).
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class I, BL
|
1 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class II, BL
|
9 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class III, BL
|
0 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class IV, BL
|
0 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class I, W4
|
0 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class II, W4
|
10 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class III, W4
|
0 Participants
|
|
Number of Participants in Each World Health Organization (WHO) Functional Class
WHO Class IV, W4
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 4Population: ITT population
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')
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Number of Participants With Change of WHO Functional Class From Previous Visit
Improved
|
0 Participants
|
|
Number of Participants With Change of WHO Functional Class From Previous Visit
Deteriorated
|
1 Participants
|
|
Number of Participants With Change of WHO Functional Class From Previous Visit
No change
|
9 Participants
|
SECONDARY outcome
Timeframe: Baseline and up to Week 4Population: ITT Population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mPAP, 1hr
|
0.5 mmHg
Standard Deviation 2.17
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mPAP, 3hr
|
1.5 mmHg
Standard Deviation 3.66
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mPAP, 24hr
|
-0.5 mmHg
Standard Deviation 3.41
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mPAP, Week4
|
1.9 mmHg
Standard Deviation 2.96
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mRAP, 1hr
|
-0.9 mmHg
Standard Deviation 2.42
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mRAP, 3hr
|
-0.1 mmHg
Standard Deviation 3.07
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mRAP, 24hr
|
0.3 mmHg
Standard Deviation 3.89
|
|
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) and Mean Right Atrial Pressure (mRAP)
mRAP, Week4
|
1.5 mmHg
Standard Deviation 3.06
|
SECONDARY outcome
Timeframe: Baseline and up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Pulmonary Vascular Resist (PVR)
1hr
|
0.204 millimeter mercury/liter/minute
Standard Deviation 2.2976
|
|
Change From Baseline in Pulmonary Vascular Resist (PVR)
3hr
|
-0.077 millimeter mercury/liter/minute
Standard Deviation 0.9716
|
|
Change From Baseline in Pulmonary Vascular Resist (PVR)
24hr
|
0.196 millimeter mercury/liter/minute
Standard Deviation 1.2514
|
|
Change From Baseline in Pulmonary Vascular Resist (PVR)
Week 4
|
0.368 millimeter mercury/liter/minute
Standard Deviation 1.5393
|
SECONDARY outcome
Timeframe: Baseline and up to Week 4Population: ITT population
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.
Outcome measures
| Measure |
FLOLAN With New Diluent
n=10 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.
|
|---|---|
|
Change From Baseline in Cardiac Output (CO)
1hr
|
-0.070 liter/minute
Standard Deviation 1.2320
|
|
Change From Baseline in Cardiac Output (CO)
3hr
|
0.460 liter/minute
Standard Deviation 1.1843
|
|
Change From Baseline in Cardiac Output (CO)
24hr
|
-0.020 liter/minute
Standard Deviation 0.8854
|
|
Change From Baseline in Cardiac Output (CO)
Week 4
|
0.408 liter/minute
Standard Deviation 0.9700
|
Adverse Events
FLOLAN With New Diluent
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
FLOLAN With New Diluent
n=10 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1 • 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.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
10.0%
1/10 • Number of events 1 • 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.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER