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Pulmonary arterial hypertension (PAH) is a rare, progressive, and life-threatening disease. In many patients, the course of PAH is a steady deterioration and reduced life expectancy.
Sildenafil was approved by the European Commission for the treatment of PAH in pediatric patients in May 2011, making it the first agent to be approved for the treatment of children with PAH. The approval was based on the largest placebo-controlled study to be conducted in this population. The recommended dose in pediatric patients aged 1 year to 17 years old is 10 mg TID in patients ≤ 20 kg and 20 mg TID for patients > 20 kg. Higher doses are not recommended in pediatrics patients.
This study is an open-label, multi-center study to investigate safety, efficacy and pharmacokinetics of sildenafil citrate in Japanese pediatric patients with PAH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sildenafil | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil | Drug | Body weight > 20 kg: 20 mg TID (60 mg/day) Body weight ≤ 20 kg: 10 mg TID (30 mg/day) Treatment duration: 16 weeks in Part 1, until until sildenafil obtained marketing approval in Part 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Week 16 | PVRI equals pulmonary vascular resistance (PVR) times body surface area (BSA) (PVRI = PVR*BSA). PVR is the resistance to blood flow through the pulmonary circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Baseline, Week 16 |
| Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 16 | It was a hemodynamic parameter and measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. | Baseline, Week 16 |
| Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Baseline, Week 4 |
| Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 8 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Sildenafil and UK-103,320 | UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Sildenafil and UK-103,320 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kitasato University Hospital | Sagamihara | Kanagawa | 252-0375 | Japan | ||
| Osaka University Hospital |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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The study was conducted at 3 sites in Japan. Data reported is based on data cut-off date of 26 December 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sildenafil | Participants received 10 milligram (mg) or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with less than or equal to (<=) 20 kilogram (kg) of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with greater than (>) 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Screening Till Week 16) |
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| Part 2(Week17 to Maximum of 119.6 Weeks) |
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Efficacy analysis set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sildenafil | Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with <= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with > 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Week 16 | PVRI equals pulmonary vascular resistance (PVR) times body surface area (BSA) (PVRI = PVR*BSA). PVR is the resistance to blood flow through the pulmonary circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points." | Posted | Mean | Standard Deviation | wood units*meter^2 | Baseline, Week 16 |
|
Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
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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 | Sildenafil | Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with <= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with > 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| Baseline, Week 8 |
| Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 16 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Baseline, Week 16 |
| Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 16 | BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation. | Baseline, Week 16 |
| Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 16 | NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage. | Baseline, Week 16 |
| Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
| Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 52 and End of Treatment (EOT) | BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation. | Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
| Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 52 and End of Treatment (EOT) | NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage. | Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs. | Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks) |
| Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs. | Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks) |
| Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 | BP measurement is recorded as supine and sitting systolic and diastolic systemic blood pressure: 1) Systolic blood pressure when heart is contracting and it is the maximum arterial pressure during contraction of left ventricle. 2) Diastolic BP when heart is relaxing and it is the minimum arterial pressure during relaxation and dilation of ventricles. Only those categories in which at least 1 participant had data were reported. | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
| Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 | Only those categories in which at least 1 participant had data were reported. | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
| Number of Participants With Laboratory Abnormalities | Laboratory abnormality criteria: Hematology (hemoglobin, hematocrit, red blood cell count [less than {<}]0.8*lower limit of normal [LLN]; platelets <0.5*LLN, greater than [>]1.75*upper limit of normal [ULN], white blood cells <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN, eosinophils, basophils, monocytes >1.2*ULN); liver function (total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein, albumin <0.8*LLN, >1.2*ULN); renal (creatinine, blood urea nitrogen >1.3*ULN); electrolytes (sodium <0.95*LLN, >1.05*ULN, potassium, chloride <0.9*LLN, >1.1*ULN; other (glucose <0.6*LLN or >1.5*ULN ); urinalysis (dipstick) urine glucose, urine protein, urine blood/Hemoglobin, [greater than or equal to {>=}1]. | Baseline up-to End of treatment (maximum duration of treatment: 119.6 weeks) |
| Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | Criteria for clinically significant abnormality in ECG parameters: Maximum corrected QT interval (QTc) from 450 millisecond (msec) to less than (<) 480 msec, Maximum QTcB interval (Bazett's Correction) from 450 msec to <480 msec, Maximum QTcF interval (Fredericia's Correction) from 450 msec to <480 msec, maximum QTc interval increase from baseline of 30 msec to <60 msec and >=60 msec. | Screening, Week 16, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
| Number of Participants With Ocular Examination Abnormalities | Ocular examination measures included external examination of the eye, funduscopy, assessments of visual acuity, and color vision. Ocular examination findings were considered abnormal based on investigator's decision. | Screening up to end of treatment (maximum duration of treatment: 119.6 weeks) |
| Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 | Baseline, Week 16 |
| Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 | Baseline, Week 16 |
| Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 | The resistance to blood flow through the pulmonary circulation is known as PVR. It is largely influenced by the caliber of the pulmonary arteries and capillaries and was measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Baseline, Week 16 |
| Change From Baseline in Right Atrial Pressure (RAP) at Week 16 | RAP is the blood pressure in the right atrium of the heart. It reflects the amount of blood returning to the heart and the ability of the heart to pump the blood into the arterial system. RAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. | Baseline, Week 16 |
| Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 | PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure. | Baseline, Week 16 |
| Change From Baseline in Cardiac Output (CO) at Week 16 | Cardiac output is simply the amount of blood pumped by the heart per minute. | Baseline, Week 16 |
| Change From Baseline in Cardiac Index (CI) at Week 16 | Cardiac index is a hemodynamic parameter that relates the cardiac output from left ventricle in one minute to BSA, thus relating heart performance to the size of the individual. CI was calculated as cardiac output in systemic circulation divided by BSA. | Baseline, Week 16 |
| Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 | The resistance to blood flow through the systemic circulation is known as SVR. This can be used in measuring blood pressure, blood flow and cardiac function and measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Baseline, Week 16 |
| Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Week 16 | SVRI equals systemic vascular resistance (SVR) times BSA. SVR is the resistance to blood flow through the systemic circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Baseline, Week 16 |
| Change From Baseline in Mixed Venous Oxygen Saturation (SvO2) at Week 16 | SvO2 is the percentage of mixed venous oxygen (amount of oxygen bound to hemoglobin in venous blood). Change from baseline in percentage of mixed venous oxygen was reported in this outcome measure. | Baseline, Week 16 |
| Change From Baseline in Arterial Oxygen Saturation (SaO2) at Week 16 | SaO2 is the percentage of arterial oxygen (amount of oxygen bound to hemoglobin in arterial blood). Change from baseline in percentage of arterial oxygen was reported in this outcome measure. | Baseline, Week 16 |
UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. |
| Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sildenafil and UK-103,320 | UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Terminal Half Life (t1/2) of Sildenafil and UK-103,320 | Terminal half-life is the time measured for the plasma concentration to decrease by one half of its original concentration. UK-103,320 was a main metabolite of sildenafil and was produced by cytochrome P450 3A4. | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Apparent Oral Clearance (CL/F) of Sildenafil | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Apparent Volume of Distribution (Vz/F) of Sildenafil | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
| Change From Baseline in Ratio of Acceleration Time to Ejection Time (AcT/ET) at Week 16 | Acceleration time and ejection time are quantitative Doppler parameters and ratio of acceleration time to ejection time is a useful tool to evaluate the severity of aortic stenosis. | Baseline, Week 16 |
| Change From Baseline in Right Ventricular Tei Index at Week 16 | The right ventricular Tei Index is an index of myocardial performance. It is defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by the ejection time. | Baseline, Week 16 |
| Change From Baseline in Right Ventricular Size at Week 16 | Baseline, Week 16 |
| Change From Baseline in Tricuspid Valve Annulus Size at Week 16 | The tricuspid valve lies between the right atrium and the right ventricle and is placed in a more apical position than the mitral valve. The annulus separates the right atrium from the right ventricle. Change from baseline in tricuspid valve annulus size (in cm) was reported in this outcome measure. | Baseline, Week 16 |
| Change From Baseline in Tricuspid Regurgitation - Pressure Gradient (TR-PG) Peak at Week 16 | Tricuspid regurgitation (insufficiency) is the failure of the tricuspid valve to close properly during systole, leading to the leaking of blood from the right ventricle into the right atrium. Change from baseline in TR-PG peak (in mmHg) was reported in this outcome measure. | Baseline, Week 16 |
| Change From Baseline in Pulmonary Regurgitation - Pressure Gradient (PR-PG) End-Diastole at Week 16 | Pulmonary regurgitation (PR) or insufficiency is a valvular heart disease characterized by an incomplete closure of the pulmonary valve leading to a diastolic reflux into the right ventricle. Change from baseline in PR-PG end-diastole (in mmHg) was reported in this outcome measure. | Baseline, Week 16 |
| Number of Participants With Pericardial Effusion | Pericardial effusion is the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography. | Baseline up to Week 16 |
| Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 16 | Tricuspid annular plane systolic excursion is a parameter depicting global right ventricular function. Change from baseline in TAPSE (in cm) was reported in this outcome measure. | Baseline, Week 16 |
| Suita |
| Osaka |
| 565-0871 |
| Japan |
| Toho University Omori Medical Center | Ōta-ku | Tokyo | 143-8541 | Japan |
| National Center for Child Health and Development | Setagaya-ku | Tokyo | 157-8535 | Japan |
| Shizuoka Children's Hospital | Shizuoka | 420-8660 | Japan |
|
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Primary | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 16 | It was a hemodynamic parameter and measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | millimeter of mercury (mmHg) | Baseline, Week 16 |
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| Primary | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Efficacy analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline, Week 4 |
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| Primary | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 8 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here,'N' (Overall number of participants analyzed) signifies those participants who were evaluable for this measure. | Posted | Number | participants | Baseline, Week 8 |
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| Primary | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 16 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, Overall Number of participants analyzed signifies those participants who were evaluable for this measure. | Posted | Number | participants | Baseline, Week 16 |
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| Primary | Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 16 | BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | picogram per milliliter | Baseline, Week 16 |
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| Primary | Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 16 | NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | picogram per milliliter | Baseline, Week 16 |
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| Secondary | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported. | Efficacy analysis set was used in this analysis. Here, 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study and 'Number analyzed' = Participants evaluable for this outcome measure for specified categories. | Posted | Count of Participants | Participants | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
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| Secondary | Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 52 and End of Treatment (EOT) | BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation. | Efficacy analysis set included all participants who received at least 1 dose of study drug.Here 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study. | Posted | Mean | Standard Deviation | picograms per milliliter | Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 52 and End of Treatment (EOT) | NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage. | EEfficacy analysis set included all participants who received at least 1 dose of study drug.Here 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study. | Posted | Mean | Standard Deviation | picograms per milliliter | Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs. | Safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs. | Safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks) |
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|
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| Secondary | Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 | BP measurement is recorded as supine and sitting systolic and diastolic systemic blood pressure: 1) Systolic blood pressure when heart is contracting and it is the maximum arterial pressure during contraction of left ventricle. 2) Diastolic BP when heart is relaxing and it is the minimum arterial pressure during relaxation and dilation of ventricles. Only those categories in which at least 1 participant had data were reported. | Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories. | Posted | Mean | Standard Deviation | mmHg | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
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| Secondary | Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 | Only those categories in which at least 1 participant had data were reported. | Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories. | Posted | Mean | Standard Deviation | beats per minute (bpm) | Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 |
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| Secondary | Number of Participants With Laboratory Abnormalities | Laboratory abnormality criteria: Hematology (hemoglobin, hematocrit, red blood cell count [less than {<}]0.8*lower limit of normal [LLN]; platelets <0.5*LLN, greater than [>]1.75*upper limit of normal [ULN], white blood cells <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN, eosinophils, basophils, monocytes >1.2*ULN); liver function (total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein, albumin <0.8*LLN, >1.2*ULN); renal (creatinine, blood urea nitrogen >1.3*ULN); electrolytes (sodium <0.95*LLN, >1.05*ULN, potassium, chloride <0.9*LLN, >1.1*ULN; other (glucose <0.6*LLN or >1.5*ULN ); urinalysis (dipstick) urine glucose, urine protein, urine blood/Hemoglobin, [greater than or equal to {>=}1]. | Safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline up-to End of treatment (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | Criteria for clinically significant abnormality in ECG parameters: Maximum corrected QT interval (QTc) from 450 millisecond (msec) to less than (<) 480 msec, Maximum QTcB interval (Bazett's Correction) from 450 msec to <480 msec, Maximum QTcF interval (Fredericia's Correction) from 450 msec to <480 msec, maximum QTc interval increase from baseline of 30 msec to <60 msec and >=60 msec. | Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories. | Posted | Count of Participants | Participants | Screening, Week 16, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Number of Participants With Ocular Examination Abnormalities | Ocular examination measures included external examination of the eye, funduscopy, assessments of visual acuity, and color vision. Ocular examination findings were considered abnormal based on investigator's decision. | Safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Screening up to end of treatment (maximum duration of treatment: 119.6 weeks) |
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| Secondary | Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Secondary | Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Secondary | Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 | The resistance to blood flow through the pulmonary circulation is known as PVR. It is largely influenced by the caliber of the pulmonary arteries and capillaries and was measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | Wood units | Baseline, Week 16 |
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| Secondary | Change From Baseline in Right Atrial Pressure (RAP) at Week 16 | RAP is the blood pressure in the right atrium of the heart. It reflects the amount of blood returning to the heart and the ability of the heart to pump the blood into the arterial system. RAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Secondary | Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 | PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Secondary | Change From Baseline in Cardiac Output (CO) at Week 16 | Cardiac output is simply the amount of blood pumped by the heart per minute. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | liter per minute | Baseline, Week 16 |
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| Secondary | Change From Baseline in Cardiac Index (CI) at Week 16 | Cardiac index is a hemodynamic parameter that relates the cardiac output from left ventricle in one minute to BSA, thus relating heart performance to the size of the individual. CI was calculated as cardiac output in systemic circulation divided by BSA. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | liter per minute per meter square | Baseline, Week 16 |
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| Secondary | Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 | The resistance to blood flow through the systemic circulation is known as SVR. This can be used in measuring blood pressure, blood flow and cardiac function and measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | Wood units | Baseline, Week 16 |
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| Secondary | Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Week 16 | SVRI equals systemic vascular resistance (SVR) times BSA. SVR is the resistance to blood flow through the systemic circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5). | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | Wood units*meter^2 | Baseline, Week 16 |
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| Secondary | Change From Baseline in Mixed Venous Oxygen Saturation (SvO2) at Week 16 | SvO2 is the percentage of mixed venous oxygen (amount of oxygen bound to hemoglobin in venous blood). Change from baseline in percentage of mixed venous oxygen was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | percentage of mixed venous oxygen | Baseline, Week 16 |
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| Secondary | Change From Baseline in Arterial Oxygen Saturation (SaO2) at Week 16 | SaO2 is the percentage of arterial oxygen (amount of oxygen bound to hemoglobin in arterial blood). Change from baseline in percentage of arterial oxygen was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | percentage of arterial oxygen | Baseline, Week 16 |
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| Other Pre-specified | Maximum Observed Plasma Concentration (Cmax) of Sildenafil and UK-103,320 | UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. | Pharmacokinetic (PK) parameter analysis set included all participants who have at least 1 of PK parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Sildenafil and UK-103,320 | UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. | PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per millimeter | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sildenafil and UK-103,320 | UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4. | PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. | Posted | Median | Full Range | hour | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Terminal Half Life (t1/2) of Sildenafil and UK-103,320 | Terminal half-life is the time measured for the plasma concentration to decrease by one half of its original concentration. UK-103,320 was a main metabolite of sildenafil and was produced by cytochrome P450 3A4. | PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Median | Full Range | hour | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Apparent Oral Clearance (CL/F) of Sildenafil | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Apparent Volume of Distribution (Vz/F) of Sildenafil | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. Here, Overall Number of participants analyzed signifies those participants who were evaluable for this measure. | Posted | Median | Full Range | liter | Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16 |
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| Other Pre-specified | Change From Baseline in Ratio of Acceleration Time to Ejection Time (AcT/ET) at Week 16 | Acceleration time and ejection time are quantitative Doppler parameters and ratio of acceleration time to ejection time is a useful tool to evaluate the severity of aortic stenosis. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | ratio | Baseline, Week 16 |
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| Other Pre-specified | Change From Baseline in Right Ventricular Tei Index at Week 16 | The right ventricular Tei Index is an index of myocardial performance. It is defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by the ejection time. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | ratio | Baseline, Week 16 |
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| Other Pre-specified | Change From Baseline in Right Ventricular Size at Week 16 | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | centimeter (cm) | Baseline, Week 16 |
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| Other Pre-specified | Change From Baseline in Tricuspid Valve Annulus Size at Week 16 | The tricuspid valve lies between the right atrium and the right ventricle and is placed in a more apical position than the mitral valve. The annulus separates the right atrium from the right ventricle. Change from baseline in tricuspid valve annulus size (in cm) was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | cm | Baseline, Week 16 |
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| Other Pre-specified | Change From Baseline in Tricuspid Regurgitation - Pressure Gradient (TR-PG) Peak at Week 16 | Tricuspid regurgitation (insufficiency) is the failure of the tricuspid valve to close properly during systole, leading to the leaking of blood from the right ventricle into the right atrium. Change from baseline in TR-PG peak (in mmHg) was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Other Pre-specified | Change From Baseline in Pulmonary Regurgitation - Pressure Gradient (PR-PG) End-Diastole at Week 16 | Pulmonary regurgitation (PR) or insufficiency is a valvular heart disease characterized by an incomplete closure of the pulmonary valve leading to a diastolic reflux into the right ventricle. Change from baseline in PR-PG end-diastole (in mmHg) was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 16 |
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| Other Pre-specified | Number of Participants With Pericardial Effusion | Pericardial effusion is the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography. | Efficacy analysis set included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to Week 16 |
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| Other Pre-specified | Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 16 | Tricuspid annular plane systolic excursion is a parameter depicting global right ventricular function. Change from baseline in TAPSE (in cm) was reported in this outcome measure. | Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points. | Posted | Mean | Standard Deviation | cm | Baseline, Week 16 |
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|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| Conjunctivitis allergic | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Chest pain | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Feeling abnormal | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
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| Ammonia increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
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| Weight increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 20.1 | Non-systematic Assessment | As the event is gender specific, only female participants were evaluated. |
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| Erection increased | Reproductive system and breast disorders | MedDRA 20.1 | Non-systematic Assessment | As the event is gender specific, only female participants were evaluated. |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Pulmonary arterial hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Visual acuity reduced transiently | Eye disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Molluscum contagiosum | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Streptococcal infection | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Blood urine present | Investigations | MedDRA 20.1 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D002318 |
| Cardiovascular Diseases |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
|
| Title | Measurements |
|---|---|
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| Baseline: Class IV |
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| Week 4: Improved |
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| Week 4: No change |
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| Week 4: Worsened |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Baseline: Class III |
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| Baseline: Class IV |
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| Week 28: Improved |
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| Week 28: No Change |
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| Week 28: Worsened |
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| Week 40: Improved |
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| Week 40: No Change |
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| Week 40: Worsened |
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| Week 52: Improved |
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| Week 52: No Change |
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| Week 52: Worsened |
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| Week 64: Improved |
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| Week 64: No Change |
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| Week 64: Worsened |
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| Week 76: Improved |
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| Week 76: No Change |
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| Week 76: Worsened |
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| Week 88: Improved |
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| Week 88: No Change |
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| Week 88: Worsened |
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| Week 100: Improved |
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| Week 100: No Change |
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| Week 100: Worsened |
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| Week 112: Improved |
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| Week 112: No Change |
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| Week 112: Worsened |
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| Week 124: Improved |
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| Week 124: No Change |
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| Week 124:Worsened |
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| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
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|
| Baseline: Sitting Systolic BP |
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| Baseline: Sitting Diastolic BP |
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| Change at Week 4: Supine Systolic BP |
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| Change at Week 4: Supine Diastolic BP |
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| Change at Week 4: Sitting Systolic BP |
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| Change at Week 4: Sitting Diastolic BP |
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| Change at Week 8: Supine Systolic BP |
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| Change at Week 8: Supine Diastolic BP |
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| Change at Week 8: Sitting Systolic BP |
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| Change at Week 8: Sitting Diastolic BP |
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| Change at Week 16: Supine Systolic BP |
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| Change at Week 16: Supine Diastolic BP |
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| Change at Week 16: Sitting Systolic BP |
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| Change at Week 16: Sitting Diastolic BP |
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| Change at Week 28: Supine Systolic BP |
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| Change at Week 28: Supine Diastolic BP |
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| Change at Week 40: Supine Systolic BP |
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| Change at Week 40: Supine Diastolic BP |
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| Change at Week 52: Supine Systolic BP |
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| Change at Week 52: Supine Diastolic BP |
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| Change at Week 64: Supine Systolic BP |
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| Change at Week 64: Supine Diastolic BP |
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| Change at Week 76: Supine Systolic BP |
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| Change at Week 76: Supine Diastolic BP |
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| Change at Week 4: Supine Heart rate |
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| Change at Week 4: Sitting Heart rate |
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| Change at Week 8: Supine Heart rate |
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| Change at Week 8: Sitting Heart rate |
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| Change at Week 16: Supine Heart rate |
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| Change at Week 16: Sitting Heart rate |
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| Change at Week 28: Supine Heart rate |
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| Change at Week 40: Supine Heart rate |
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| Change at Week 52: Supine Heart rate |
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| Change at Week 64: Supine Heart rate |
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| Change at Week 76: Supine Heart rate |
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| Week 52 |
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| End of Treatment |
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| Change at Week 16: Systolic Pressure |
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| Change at Week 16: Diastolic Pressure |
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| Change at Week 16: Systolic Pressure |
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| Change at Week 16: Diastolic Pressure |
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