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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019547-19 | EudraCT Number |
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Ongoing juvenile rat toxicology studies.
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A 6-month (24-week), randomized, open label evaluation of the safety, tolerability, and efficacy of a high and low dose ambrisentan (adjusted for body weight) treatment group in subjects aged 8 years up to 18 years with pulmonary arterial hypertension (PAH). An additional objective is to determine the ambrisentan population pharmacokinetics in the paediatric population. The study will include a screening/baseline period and a treatment period. The treatment period will be 24 weeks or until the subject's clinical condition deteriorates to the point that alternative/additional treatment is necessary. Patients who participate in the study and in whom continued treatment with ambrisentan is desired will be eligible to enrol into a long term follow-up study. The primary comparison will be the safety and tolerability of the two ambrisentan dose groups (Low vs. High) in the paediatric PAH population The secondary comparison will be the change from baseline for the efficacy parameters between the two treatment groups.
Pulmonary arterial hypertension (PAH) is a rare, progressive, highly debilitating disease characterized by vascular obstruction and the variable presence of vasoconstriction, leading to increased pulmonary vascular resistance and right-sided heart failure. If left untreated, PAH ultimately leads to right ventricular failure and death; adult subjects have a median survival of 2.8 years without treatment. Epidemiological estimates vary but prevalence in Europe is thought to be of the order of 15 cases per million. Large scale epidemiology studies of PAH in children have not been conducted and there is no or limited outcome data in pediatric PAH patients. A register in France (1995-1996) estimates the prevalence in children is as low as 3.7 cases per million. In a national, comprehensive country wide survey of the epidemiology of idiopathic PAH (IPAH) management and survival in the United Kingdom (UK) the incidence was 0.48 cases per million children per year and the prevalence was 2.1 cases per million children.
Ambrisentan (VOLIBRIS™ tablets) is an endothelin receptor antagonist (ERA) marketed in the European Union (EU) and some other countries by GlaxoSmithKline (GSK) and in the United States as LETAIRIS® by Gilead Sciences Inc. Ambrisentan is indicated for the treatment of adult patients with PAH to improve exercise capacity, decrease the symptoms of PAH, and delay clinical worsening.
The primary purpose of this paediatric study is to provide clinically relevant information on the safety and pharmacokinetic profile of ambrisentan in children with the most common causes of PAH in this age group. The design of the study is also intended to provide information to guide dose selection and supportive efficacy data in this age group. Despite the fact that none of the currently available adult treatments are licensed for use in children <12 yrs, (with the exception of bosentan which was recently approved for use in paediatric population from 2 years of age) they are widely used off label. This study will provide useful prescribing information to the medical community for treating this orphan disease in children in this environment of rapidly changing medical practice.
This study is part of a Paediatric Investigational Plan (PIP; EMEA-000434-PIP01-08) agreed with the European Medicines Agency's Paediatric Committee (PDCO).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose Ambrisentan | Experimental | body weight 20 to 35 kg - 2.5 mg; body weight 35 kg and over - 5.0 mg |
|
| High Dose Ambrisentan | Experimental | body weight 20 to 35 kg - 5.0 mg; body weight 35 to 50 kg - 7.5 mg; body weight 50 kg and over - 10.0 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ambrisentan - low dose | Drug | body weight 20 to 35 kg - 2.5 mg; body weight 35 kg and over - 5.0 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Treatment-emergent Adverse Events (SAEs) | AEs defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs 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 or incapacity, or is a congenital anomaly or birth defect, medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention as per medical or scientific judgement and events of drug-induced liver injury with hyperbilirubinaemia. Safety population comprised of all randomized participants who received at least 1 dose of study drug. | Up to 24 Weeks |
| Number of Participants With Post Baseline Potential Clinical Importance (PCI) Value for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin and Creatinine | Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, AST, GGT, total bilirubin and creatinine. PCI ranges were <3 times the upper limit of normal (ULN), <34.2 Micromoles per liter (UMOL/L) for total bilirubin and <176.8 (UMOL/L) for creatinine. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hemoglobin | Blood samples were collected from participants for analysis of following hematology parameters: hemoglobin. PCI ranges were Males: 98 to180 grams per liter (G/L), Females: 91 to 161 (G/L) for hemoglobin. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hematocrit |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Participant's 6MWD data has been presented into three categories as overall, with oxygen use and without oxygen use. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. NA indicates that standard deviation could not be calculated for single participant. Intent-to-Treat (ITT) population consist of all randomized participants who received at least one dose of study drug. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Aurora | Colorado | 80045 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37332660 | Derived | Ivy D, Beghetti M, Juaneda-Simian E, Miller D, Lukas MA, Ioannou C, Okour M, Narita J, Berger RMF. A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years. J Pediatr X. 2020 Sep 22;5:100055. doi: 10.1016/j.ympdx.2020.100055. eCollection 2020 Spring. | |
| 36579617 |
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A total of 41 participants were enrolled and randomized.
This study investigated the safety and efficacy of a high and low dose ambrisentan (adjusted as per participants body weight) administered orally in participants aged 8 to 18 years with pulmonary arterial hypertension (PAH).
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Ambrisentan | Participants received ambrisentan low dose tablet either 2.5 milligram (mg) or 5 mg orally once daily for 24 weeks. |
| FG001 | High Dose Ambrisentan | Participants received ambrisentan high dose tablet either 5 mg, 7.5 mg or 10 mg orally once daily for 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2018 | Aug 7, 2019 |
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| Ambrisentan - high dose | Drug | body weight 20 to 35 kg - 5.0 mg; body weight 35 to 50 kg - 7.5 mg; body weight 50 kg and over - 10.0 mg |
|
Blood samples were collected from participants for analysis of following hematology parameter: hematocrit. PCI ranges were males: <0.32 to >0.54, females: <0.29 to >0.506 proportion of red blood cells in blood for hematocrit. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. |
| Up to 24 Weeks |
| Number of Participants With Post Baseline PCI Value for Hematology Parameter: Platelet Count | Blood samples were collected from participants for analysis of following hematology parameter: platelet count. PCI ranges were 100 to 400 for Giga cells per liter platelet count. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Number of Participants With Abnormal Value for Physical Examination Parameter: Liver Size | Physical examination included measurement of liver size. Any abnormal enlargement or reduction in the size of the liver is reported. | Week 12 and 24 |
| Number of Participants With Abnormal Value for Physical Examination Parameter: Jugular Venous Pressure | Physical examination of participants jugular venous pressure is measured. | Week 12 and 24 |
| Number of Participants With Abnormal Value for Physical Examination Parameter: Peripheral Edema | Physical examination of paricipants peripheral edema is measured. Day 1 was considered as Baseline. | Week 12 and 24 |
| Number of Participants With Abnormal Value for Physical Examination Parameter: Ascites | Physcial examination of paricipants ascites was measured. Day 1 was considered as Baseline. | Week 12 and 24 |
| Percentage of Physical Examination Parameter: Saturated Oxygen Level | Physical examination of participants saturated oxygen level was measured. Day 1 was considered as Baseline. | Week 12 and 24 |
| Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges were <80 to >160 millimeters of mercury (mmHg) for SDP and <40 to >110 mmHg for DBP. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Heart Rate | Heart rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges were <50 to >120 beats per minute (beats/min). Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Weight | Weight of the participants was measured. PCI ranges were <20 kilogram (kg) for weight. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Up to 24 Weeks |
| Change From Baseline of Pubertal Development: Men- Testicular Volume (TV) at Weeks 12 and 24 | Testicular volume was assessed by Prader's orchiodometer and the assessment was performed by a pediatric endocrinologist using the Tanner's criteria. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 12 and 24 |
| Change From Baseline in Plasma Endocrine Parameter - Female : Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at Weeks 12 and 24 | FSH and LH level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 12 and 24 |
| Change From Baseline in Plasma Endocrine Parameter - Female : Inhibin B at Weeks 12 and 24 | Inhibin B level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 12 and 24 |
| Change From Baseline in Plasma Endocrine Parameter - Female : Sex Hormone Binding Globulin at Weeks 12 and 24 | Sex hormone binding globulin level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 12 and 24 |
| Baseline, Weeks 4, 8, 12, 16, 20 and 24 |
| Time to the First Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | Time to clinical worsening of PAH is defined as the time from randomization to the first occurrence of death or placed for lung transplant, hospitalization due to PAH deterioration, addition or increased dose of other targeted PAH therapeutic agents like prostanoids and PDE-5 inhibitors) and/or atrial septostomy, other PAH related deterioration identified by increase in WHO functional class, deterioration in exercise testing and clinical signs or symptoms of right sided heart failure. | Up to Week 24 |
| Change From Baseline in Subject Global Assessment to Week 24 Using the SF-10 Health Survey for Children | Short-form 10 (SF-10) Health Survey for Children is a 10-item parent-completed health assessment that measures physical and psychosocial functioning for children ages five and over. Each item has either 4, 5 or 6 response choices with associated point systems. Two summary scores were calculated: a Physical Summary Score (PHS) and a Psychosocial Summary Score (PSS) with a range of 5 to 30 points for each 5-item score. This aggregated point score was then standardized and transformed to a norm-based scoring metric in accordance with the developer's algorithms using associated mean and standard deviation derived from 2006 sample data. This generated the final standardized norm-based scores for PHS (range -10.90 to 57.21) and for PSS (range 8.81 to 62.28), respectively. A higher value on each summary score indicates better functioning. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline and Week 24 |
| Change From Baseline in World Health Organization (WHO) Functional Class to Week 24 | PAH was classified by WHO functional class (FC) at specific time points. There were four WHO FC grades based on severity of PAH symptoms (Class I=none, Class IV=most severe). Grades were then mapped to numeric scale, for which scores ranged from 1 to 4 (Class I=1 and Class IV=4). Score at Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 4, 8, 12, 16, 20 and 24 |
| Ratio to Baseline in Plasma N-terminal Pro-B Type Natriuretic Peptide (NT-Pro BNP) Concentration at Week 24 | NT-Pro BNP plasma concentrations were determined at specific time points. Geometric mean and SD logs has been presented. Day 1 was considered as Baseline. Ratio to Baseline is expressed as percentage change from Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Baseline, Week 12 and 24 |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| GSK Investigational Site | Ann Arbor | Michigan | 48109-4204 | United States |
| GSK Investigational Site | New York | New York | 10032 | United States |
| GSK Investigational Site | Guymallen | Mendoza Province | 5521 | Argentina |
| GSK Investigational Site | Ciudad de Buenos Aires | 1118 | Argentina |
| GSK Investigational Site | Córdoba | 5000 | Argentina |
| GSK Investigational Site | Paris | 75743 | France |
| GSK Investigational Site | Pessac | 33604 | France |
| GSK Investigational Site | Toulouse | 31059 | France |
| GSK Investigational Site | Erlangen | Bavaria | 91054 | Germany |
| GSK Investigational Site | Giessen | Hesse | 35385 | Germany |
| GSK Investigational Site | Berlin | 13353 | Germany |
| GSK Investigational Site | Budapest | 1096 | Hungary |
| GSK Investigational Site | Rome | Lazio | 00165 | Italy |
| GSK Investigational Site | San Donato Milanese (MI) | Lombardy | 20097 | Italy |
| GSK Investigational Site | Kanagawa | 232-8555 | Japan |
| GSK Investigational Site | Osaka | 565-0871 | Japan |
| GSK Investigational Site | Tokyo | 104-8560 | Japan |
| GSK Investigational Site | Tokyo | 143-8541 | Japan |
| GSK Investigational Site | Kemerovo | 650002 | Russia |
| GSK Investigational Site | Moscow | 125412 | Russia |
| GSK Investigational Site | Novosibirsk | 630055 | Russia |
| GSK Investigational Site | Madrid | 28046 | Spain |
| Okour M, Thapar MM, Farrell C, Lukas MA, Beghetti M, Beerahee M. Pediatric Population Pharmacokinetic Modeling and Exposure-Response Analysis of Ambrisentan in Pulmonary Arterial Hypertension and Comparison With Adult Data. J Clin Pharmacol. 2023 May;63(5):593-603. doi: 10.1002/jcph.2199. Epub 2023 Jan 29. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose Ambrisentan | Participants received ambrisentan low dose tablet either 2.5 mg or 5 mg orally once daily for 24 weeks. |
| BG001 | High Dose Ambrisentan | Participants received ambrisentan high dose tablet either 5 mg, 7.5 mg or 10 mg orally once daily for 24 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | 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 | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Treatment-emergent Adverse Events (SAEs) | AEs defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs 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 or incapacity, or is a congenital anomaly or birth defect, medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention as per medical or scientific judgement and events of drug-induced liver injury with hyperbilirubinaemia. Safety population comprised of all randomized participants who received at least 1 dose of study drug. | Safety Population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Post Baseline Potential Clinical Importance (PCI) Value for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin and Creatinine | Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, AST, GGT, total bilirubin and creatinine. PCI ranges were <3 times the upper limit of normal (ULN), <34.2 Micromoles per liter (UMOL/L) for total bilirubin and <176.8 (UMOL/L) for creatinine. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety Population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hemoglobin | Blood samples were collected from participants for analysis of following hematology parameters: hemoglobin. PCI ranges were Males: 98 to180 grams per liter (G/L), Females: 91 to 161 (G/L) for hemoglobin. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Post Baseline PCI Value for Hematology Parameter: Hematocrit | Blood samples were collected from participants for analysis of following hematology parameter: hematocrit. PCI ranges were males: <0.32 to >0.54, females: <0.29 to >0.506 proportion of red blood cells in blood for hematocrit. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Post Baseline PCI Value for Hematology Parameter: Platelet Count | Blood samples were collected from participants for analysis of following hematology parameter: platelet count. PCI ranges were 100 to 400 for Giga cells per liter platelet count. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Abnormal Value for Physical Examination Parameter: Liver Size | Physical examination included measurement of liver size. Any abnormal enlargement or reduction in the size of the liver is reported. | Safety population. Only those participants with available data at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and 24 |
|
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| Primary | Number of Participants With Abnormal Value for Physical Examination Parameter: Jugular Venous Pressure | Physical examination of participants jugular venous pressure is measured. | Safety population. Only those participants with available data at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and 24 |
|
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| Primary | Number of Participants With Abnormal Value for Physical Examination Parameter: Peripheral Edema | Physical examination of paricipants peripheral edema is measured. Day 1 was considered as Baseline. | Safety population. Only those participants with available data at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and 24 |
|
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| Primary | Number of Participants With Abnormal Value for Physical Examination Parameter: Ascites | Physcial examination of paricipants ascites was measured. Day 1 was considered as Baseline. | Safety population. Only those participants with available data at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and 24 |
|
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| Primary | Percentage of Physical Examination Parameter: Saturated Oxygen Level | Physical examination of participants saturated oxygen level was measured. Day 1 was considered as Baseline. | Safety population. Only those participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Percentage of oxygen saturation | Week 12 and 24 |
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| Primary | Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges were <80 to >160 millimeters of mercury (mmHg) for SDP and <40 to >110 mmHg for DBP. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
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| Primary | Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Heart Rate | Heart rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges were <50 to >120 beats per minute (beats/min). Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
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| Primary | Number of Participants With Post Baseline PCI Value for Vital Signs Parameter: Weight | Weight of the participants was measured. PCI ranges were <20 kilogram (kg) for weight. Only those parameters having any time post-Baseline PCI values were presented. Day 1 was considered as Baseline. | Safety population | Posted | Count of Participants | Participants | Up to 24 Weeks |
|
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| Primary | Change From Baseline of Pubertal Development: Men- Testicular Volume (TV) at Weeks 12 and 24 | Testicular volume was assessed by Prader's orchiodometer and the assessment was performed by a pediatric endocrinologist using the Tanner's criteria. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Safety population. Only those male participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Milliliter | Baseline, Week 12 and 24 |
|
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| Primary | Change From Baseline in Plasma Endocrine Parameter - Female : Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at Weeks 12 and 24 | FSH and LH level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Safety population. Only those female participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | International unit per Liter | Baseline, Week 12 and 24 |
|
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| Primary | Change From Baseline in Plasma Endocrine Parameter - Female : Inhibin B at Weeks 12 and 24 | Inhibin B level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Safety population. Only those female participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Nanogram per liter | Baseline, Week 12 and 24 |
|
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| Primary | Change From Baseline in Plasma Endocrine Parameter - Female : Sex Hormone Binding Globulin at Weeks 12 and 24 | Sex hormone binding globulin level of participants were measured. Only those parameters having status - overall were presented. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Safety population. Only those female participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Milliliter | Baseline, Week 12 and 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test | Participant's 6MWD data has been presented into three categories as overall, with oxygen use and without oxygen use. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. NA indicates that standard deviation could not be calculated for single participant. Intent-to-Treat (ITT) population consist of all randomized participants who received at least one dose of study drug. | Intent-to-treat population. Only those participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Meters | Baseline, Weeks 4, 8, 12, 16, 20 and 24 |
|
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| Secondary | Time to the First Clinical Worsening of Pulmonary Arterial Hypertension (PAH) | Time to clinical worsening of PAH is defined as the time from randomization to the first occurrence of death or placed for lung transplant, hospitalization due to PAH deterioration, addition or increased dose of other targeted PAH therapeutic agents like prostanoids and PDE-5 inhibitors) and/or atrial septostomy, other PAH related deterioration identified by increase in WHO functional class, deterioration in exercise testing and clinical signs or symptoms of right sided heart failure. | Intent-to-treat population. Only those participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Days | Up to Week 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Subject Global Assessment to Week 24 Using the SF-10 Health Survey for Children | Short-form 10 (SF-10) Health Survey for Children is a 10-item parent-completed health assessment that measures physical and psychosocial functioning for children ages five and over. Each item has either 4, 5 or 6 response choices with associated point systems. Two summary scores were calculated: a Physical Summary Score (PHS) and a Psychosocial Summary Score (PSS) with a range of 5 to 30 points for each 5-item score. This aggregated point score was then standardized and transformed to a norm-based scoring metric in accordance with the developer's algorithms using associated mean and standard deviation derived from 2006 sample data. This generated the final standardized norm-based scores for PHS (range -10.90 to 57.21) and for PSS (range 8.81 to 62.28), respectively. A higher value on each summary score indicates better functioning. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Intent-to-treat population. Only those participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline and Week 24 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in World Health Organization (WHO) Functional Class to Week 24 | PAH was classified by WHO functional class (FC) at specific time points. There were four WHO FC grades based on severity of PAH symptoms (Class I=none, Class IV=most severe). Grades were then mapped to numeric scale, for which scores ranged from 1 to 4 (Class I=1 and Class IV=4). Score at Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Intent-to-treat population. Only those participants with available data at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, Week 4, 8, 12, 16, 20 and 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Ratio to Baseline in Plasma N-terminal Pro-B Type Natriuretic Peptide (NT-Pro BNP) Concentration at Week 24 | NT-Pro BNP plasma concentrations were determined at specific time points. Geometric mean and SD logs has been presented. Day 1 was considered as Baseline. Ratio to Baseline is expressed as percentage change from Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. | Intent-to-treat population. Only those participants with available data at the specified time points were analyzed. | Posted | Geometric Mean | Standard Deviation | Percentage Change | Baseline, Week 12 and 24 |
|
|
On-treatment serious adverse events (SAEs) and non serious AEs were collected from the start of study treatment up to 24 weeks
Safety Population was used. Safety Population comprised of all randomized participants who received at least one dose of a study drug
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low Dose Ambrisentan | Participants received ambrisentan low dose tablet either 2.5 mg or 5 mg orally once daily for 24 weeks. | 1 | 21 | 6 | 21 | 16 | 21 |
| EG001 | High Dose Ambrisentan | Participants received ambrisentan high dose tablet either 5 mg, 7.5 mg or 10 mg orally once daily for 24 weeks. | 0 | 20 | 2 | 20 | 16 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure acute | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Right ventricular failure | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Device breakage | Product Issues | MedDRA 21.0 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Heparin-induced thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cyanosis | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Feb 2, 2011 | Aug 8, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C467894 | ambrisentan |
Not provided
Not provided
Not provided
| Male |
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| American Indian or Alaskan Native |
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| Asian - Central/South Asian Heritage |
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| Asian - East Asian Heritage |
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| Asian - Japanese Heritage |
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| Asian - South East Asian Heritage |
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| White - White/Caucasian/European Heritage |
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Participants received ambrisentan high dose tablet either 5 mg, 7.5 mg or 10 mg orally once daily for 24 weeks.
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